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Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs).
SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations.
Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures.
The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.
Clostridioides difficile infection (CDI) can be prevented through infection prevention practices and antibiotic stewardship. Diagnostic stewardship (ie, strategies to improve use of microbiological testing) can also improve antibiotic use. However, little is known about the use of such practices in US hospitals, especially after multidisciplinary stewardship programs became a requirement for US hospital accreditation in 2017. Thus, we surveyed US hospitals to assess antibiotic stewardship program composition, practices related to CDI, and diagnostic stewardship.
Surveys were mailed to infection preventionists at 900 randomly sampled US hospitals between May and October 2017. Hospitals were surveyed on antibiotic stewardship programs; CDI prevention, treatment, and testing practices; and diagnostic stewardship strategies. Responses were compared by hospital bed size using weighted logistic regression.
Overall, 528 surveys were completed (59% response rate). Almost all (95%) responding hospitals had an antibiotic stewardship program. Smaller hospitals were less likely to have stewardship team members with infectious diseases (ID) training, and only 41% of hospitals met The Joint Commission accreditation standards for multidisciplinary teams. Guideline-recommended CDI prevention practices were common. Smaller hospitals were less likely to use high-tech disinfection devices, fecal microbiota transplantation, or diagnostic stewardship strategies.
Following changes in accreditation standards, nearly all US hospitals now have an antibiotic stewardship program. However, many hospitals, especially smaller hospitals, appear to struggle with access to ID expertise and with deploying diagnostic stewardship strategies. CDI prevention could be enhanced through diagnostic stewardship and by emphasizing the role of non–ID-trained pharmacists and clinicians in antibiotic stewardship.
The SUPEREDEN3 study, a phase II randomized controlled trial, suggests that social recovery therapy (SRT) is useful in improving functional outcomes in people with first episode psychosis. SRT incorporates cognitive behavioural therapy (CBT) techniques with case management and employment support, and therefore has a different emphasis to traditional CBT for psychosis, requiring a new adherence tool.
This paper describes the SRT adherence checklist and content of the therapy delivered in the SUPEREDEN3 trial, outlining the frequency of SRT techniques and proportion of participants who received a full therapy dose. It was hypothesized that behavioural techniques would be used frequently, consistent with the behavioural emphasis of SRT.
Research therapists completed an adherence checklist after each therapy session, endorsing elements of SRT present. Data from 1236 therapy sessions were reviewed to determine whether participants received full, partial or no therapy dose.
Of the 75 participants randomized to receive SRT, 57.3% received a full dose, 24% a partial dose, and 18.7% received no dose. Behavioural techniques were endorsed in 50.5% of sessions, with cognitive techniques endorsed in 34.9% of sessions.
This report describes an adherence checklist which should be used when delivering SRT in both research and clinical practice. As hypothesized, behavioural techniques were a prominent feature of the SRT delivered in SUPEREDEN3, consistent with the behavioural emphasis of the approach. The use of this adherence tool would be considered essential for anyone delivering SRT looking to ensure adherence to the model.
Collaborative programs have helped reduce catheter-associated urinary tract infection (CAUTI) rates in community-based nursing homes. We assessed whether collaborative participation produced similar benefits among Veterans Health Administration (VHA) nursing homes, which are part of an integrated system.
This study included 63 VHA nursing homes enrolled in the “AHRQ Safety Program for Long-Term Care,” which focused on practices to reduce CAUTI.
Changes in CAUTI rates, catheter utilization, and urine culture orders were assessed from June 2015 through May 2016. Multilevel mixed-effects negative binomial regression was used to derive incidence rate ratios (IRRs) representing changes over the 12-month program period.
There was no significant change in CAUTI among VHA sites, with a CAUTI rate of 2.26 per 1,000 catheter days at month 1 and a rate of 3.19 at month 12 (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.67–1.44). Results were similar for catheter utilization rates, which were 11.02% at month 1 and 11.30% at month 12 (IRR, 1.02; 95% CI, 0.95–1.09). The numbers of urine cultures per 1,000 residents were 5.27 in month 1 and 5.31 in month 12 (IRR, 0.93; 95% CI, 0.82–1.05).
No changes in CAUTI rates, catheter use, or urine culture orders were found during the program period. One potential reason was the relatively low baseline CAUTI rate, as compared with a cohort of community-based nursing homes. This low baseline rate is likely related to the VHA’s prior CAUTI prevention efforts. While broad-scale collaborative approaches may be effective in some settings, targeting higher-prevalence safety issues may be warranted at sites already engaged in extensive infection prevention efforts.
There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems.
To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious.
Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks.
The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety.
Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed.
To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing.
We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria.
PARTICIPANTS AND SETTING
Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital.
Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit.
In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%).
Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
This new book will provide a ground breaking discussion of a major but little considered issue - the silence of the archive: why archives, sometimes seen as the repositories of truth, often fail to satisfy users because they do not contain information which they expect to find. Silences range from details of individuals' lives to records of state oppression or of intelligence operations. The book brings together ideas from a wide range of fields, from contemporary history through family history research to Shakespearian studies. It describes why there are these silences, what the impact of them is, how researchers have responded to them and what the silence of the archive means for researchers in the digital age.
Research was conducted from 2011 to 2014 to determine weed population
dynamics and frequency of glyphosate-resistant (GR) Palmer amaranth with
herbicide programs consisting of glyphosate, dicamba, and residual
herbicides in dicamba-tolerant cotton. Five treatments were maintained in
the same plots over the duration of the experiment: three sequential POST
applications of glyphosate with or without pendimethalin plus diuron PRE;
three sequential POST applications of glyphosate plus dicamba with and
without the PRE herbicides; and a POST application of glyphosate plus
dicamba plus acetochlor followed by one or two POST applications of
glyphosate plus dicamba without PRE herbicides. Additional treatments
included alternating years with three sequential POST applications of
glyphosate only and glyphosate plus dicamba POST with and without PRE
herbicides. The greatest population of Palmer amaranth was observed when
glyphosate was the only POST herbicide throughout the experiment. Although
diuron plus pendimethalin PRE in a program with only glyphosate POST
improved control during the first 2 yr, these herbicides were ineffective by
the final 2 yr on the basis of weed counts from soil cores. The lowest
population of Palmer amaranth was observed when glyphosate plus dicamba were
applied regardless of PRE herbicides or inclusion of acetochlor POST.
Frequency of GR Palmer amaranth was 8% or less when the experiment was
initiated. Frequency of GR Palmer amaranth varied by herbicide program
during 2012 but was similar among all herbicide programs in 2013 and 2014.
Similar frequency of GR Palmer amaranth across all treatments at the end of
the experiment most likely resulted from pollen movement from Palmer
amaranth treated with glyphosate only to any surviving female plants
regardless of PRE or POST treatment. These data suggest that GR Palmer
amaranth can be controlled by dicamba and that dicamba is an effective
alternative mode of action to glyphosate in fields where GR Palmer amaranth
Various transmission routes contribute to spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated (“CRKP readmission”) potentially contribute to transmission of CRKP.
To evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKLe).
Cohort study from December 24, 2011, through July 1, 2013.
Multicenter consortium of acute care hospitals in the Great Lakes region.
All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP-positive culture.
All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models.
Fifty-six (20%) of 287 patients who were discharged alive had a CRKP readmission. History of malignancy was associated with CRKP readmission (adjusted odds ratio [adjusted OR], 3.00 [95% CI, 1.32–6.65], P<.01). During the index hospitalization, 160 patients (56%) received antibiotic treatment against CRKP; the choice of regimen was associated with CRKP readmission (P=.02). Receipt of tigecycline-based therapy (adjusted OR, 5.13 [95% CI, 1.72–17.44], using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission.
Hospitalized patients with CRKP—specifically those with a history of malignancy—are at high risk of readmission with recurrent CRKP infection or colonization. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk.
Infect. Control Hosp. Epidemiol. 2016;37(3):281–288
Social disability is a hallmark of severe mental illness yet individual
differences and factors predicting outcome are largely unknown.
To explore trajectories and predictors of social recovery following a
first episode of psychosis (FEP).
A sample of 764 individuals with FEP were assessed on entry into early
intervention in psychosis (EIP) services and followed up over 12 months.
Social recovery profiles were examined using latent class growth
Three types of social recovery profile were identified: Low Stable (66%),
Moderate-Increasing (27%), and High-Decreasing (7%). Poor social recovery
was predicted by male gender, ethnic minority status, younger age at
onset of psychosis, increased negative symptoms, and poor premorbid
Social disability is prevalent in FEP, although distinct recovery
profiles are evident. Where social disability is present on entry into
EIP services it can remain stable, highlighting a need for targeted
Early intervention services (EIS) comprise low-stigma, youth-friendly mental health teams for young people undergoing first-episode psychosis (FEP). Engaging with the family of the young person is central to EIS policy and practice.
By analysing carers' accounts of their daily lives and affective challenges during a relative's FEP against the background of wider research into EIS, this paper explores relationships between carers' experiences and EIS.
Semi-structured longitudinal interviews with 80 carers of young people with FEP treated through English EIS.
Our data suggest that EIS successfully aid carers to support their relatives, particularly through the provision of knowledge about psychosis and medications. However, paradoxical ramifications of these user-focused engagements also emerge; they risk leaving carers' emotions unacknowledged and compounding an existing lack of help-seeking.
By focusing on EIS's engagements with carers, this paper draws attention to an urgent broader question: as a continuing emphasis on care outside the clinic space places family members at the heart of the care of those with severe mental illness, we ask: who can, and should, support carers, and in what ways?