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Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critical but can lead to overdiagnosis and overtreatment.
We investigated healthcare provider (HCP) perceptions and challenges associated with VAP diagnosis, and we sought to identify opportunities for diagnostic stewardship.
We conducted a qualitative study of 30 HCPs at a tertiary-care hospital. Participants included attending physicians, residents and fellows (trainees), advanced practice providers (APPs), and pharmacists. Interviews were composed of open-ended questions in 4 sections: (1) clinical suspicion and thresholds for respiratory culture ordering, (2) preferences for respiratory sample collection, (3) culture report interpretation, and (4) VAP diagnosis and treatment. Interviews transcripts were analyzed using Nvivo 12 software, and responses were organized into themes.
Overall, 10 attending physicians (75%) and 16 trainees (75%) trainees and APPs believed they were overdiagnosing VAP; this response was frequent among HCPs in practice 5–10 years (91%, n = 12). Increased identification of bacteria as a result of frequent respiratory culturing, misinterpretation of culture data, and fear of missing diagnosis were recognized as drivers of overdiagnosis and overtreatment. Although most HCPs rely on clinical and radiographic changes to initiate work-up, the fear of missing a diagnosis leads to sending cultures even in the absence of those changes.
HCPs believe that VAP overdiagnosis and overtreatment are common due to fear of missing diagnosis, overculturing, and difficulty distinguishing colonization from infection. Although we identified opportunities for diagnostic stewardship, interventions influencing the ordering of cultures and starting antimicrobials will need to account for strongly held beliefs and ICU practices.
Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
The perinatal period is a vulnerable time for the development of psychopathology, particularly mood and anxiety disorders. In the study of maternal anxiety, important questions remain regarding the association between maternal anxiety symptoms and subsequent child outcomes. This study examined the association between depressive and anxiety symptoms, namely social anxiety, panic, and agoraphobia disorder symptoms during the perinatal period and maternal perception of child behavior, specifically different facets of development and temperament. Participants (N = 104) were recruited during pregnancy from a community sample. Participants completed clinician-administered and self-report measures of depressive and anxiety symptoms during the third trimester of pregnancy and at 16 months postpartum; child behavior and temperament outcomes were assessed at 16 months postpartum. Child development areas included gross and fine motor skills, language and problem-solving abilities, and personal/social skills. Child temperament domains included surgency, negative affectivity, and effortful control. Hierarchical multiple regression analyses demonstrated that elevated prenatal social anxiety symptoms significantly predicted more negative maternal report of child behavior across most measured domains. Elevated prenatal social anxiety and panic symptoms predicted more negative maternal report of child effortful control. Depressive and agoraphobia symptoms were not significant predictors of child outcomes. Elevated anxiety symptoms appear to have a distinct association with maternal report of child development and temperament. Considering the relative influence of anxiety symptoms, particularly social anxiety, on maternal report of child behavior and temperament can help to identify potential difficulties early on in mother–child interactions as well as inform interventions for women and their families.
The mind and body are connected in a myriad of ways that we as healthcare providers still do not fully comprehend. Recent research has demonstrated that there are biological, neurocognitive, psychological, spiritual, and social features of diseases and disorders, and there has been movement within the healthcare field toward the integrative biopsychosocial approach in the provision of healthcare services. Addressing these aspects allows the healthcare provider to tailor treatment to a patient’s unique needs. This chapter covers interventions in the areas of positive neuropsychology/cognitive health, cognitive rehabilitation, and neuroenhancement.
UK trees require increased conservation efforts due to sparse and fragmented populations. Ex situ conservation, including seed banking, can be used to better manage these issues. We conducted accelerated ageing tests on seeds of 22 UK native woody species, in order to assess their likely longevity and optimize their conservation in a seed bank. Germination at four ageing time points was determined to construct survival curves, and it was concluded that multiple samples within a species showed comparable responses for most species tested, except for Fraxinus excelsior. Of all species studied, one could be classified as very short-lived, four as short-lived and 17 as medium, with none exceeding the medium category. The most important finding of this manuscript is that although some taxonomic trends were observed, the results indicate the need for caution when making broad conclusions on potential seed storage life at a species, genus or family level. Longevity predictions were compared to actual performance of older collections held in long-term storage at the Millennium Seed Bank, Kew. Although most collections remain high in viability in storage after more than 20 years, for short-lived species at least, there is some indication that accelerated ageing predicts longevity in seed bank conditions. For species with reduced potential longevity, such as Fagus sylvatica and Ulmus glabra, additional storage options are recommended for long-term gene banking.
The transmission rate of methicillin-resistant Staphylococcus aureus (MRSA) to gloves or gowns of healthcare personnel (HCP) caring for MRSA patients in a non–intensive care unit setting was 5.4%. Contamination rates were higher among HCP performing direct patient care and when patients had detectable MRSA on their body. These findings may inform risk-based contact precautions.
To evaluate whether clinical cultures are an appropriate surrogate for surveillance cultures to measure the effect of interventions on the incidence of MRSA and VRE in the hospital.
Cross-sectional and quasi-experimental, retrospective analysis
Setting and population:
Convenience sample of patients admitted between January 1, 2002, and June 31, 2011, to the medical intensive care unit (MICU) and surgical intensive care unit (SICU) of an acute-care hospital in the United States.
Asynchronously in the MICU and SICU, we introduced (1) universal glove and gown use, (2) bundled intervention to prevent central-line–associated bloodstream infection, and (3) daily chlorhexidine gluconate bathing.
We observed a statistically significant correlation between surveillance and clinical culture-based incidence rates of MRSA in the MICU (0.32; P < .001) and the SICU (0.37; P < .001) but not for VRE in either the MICU (0.16, P = .11) or the SICU (0.15; P = .12). For VRE, but not for MRSA, incidence density rates based on surveillance cultures were 2- to 4-fold higher than for clinical cultures. When evaluating the impacts of the interventions, different effect estimates were noted for universal glove and gown use on MRSA acquisition in MICU, and for VRE acquisition in both the MICU and the SICU based on surveillance versus clinical cultures.
For multidrug-resistant organism acquisition, surveillance cultures should be used when feasible because clinical cultures may not be an appropriate surrogate. Clinical or surveillance-based end points for infection control interventions should reflect the conceptual model from colonization to infection and where an intervention might have an effect, rather than considering them interchangeable.
This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
We studied the association between chlorhexidine gluconate (CHG) concentration on skin and resistant bacterial bioburden. CHG was almost always detected on the skin, and detection of methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant Enterococcus on skin sites was infrequent. However, we found no correlation between CHG concentration and bacterial bioburden.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
In cluster-randomized trials (CRT), groups rather than individuals are randomized to interventions. The aim of this study was to present critical design, implementation, and analysis issues to consider when planning a CRT in the healthcare setting and to synthesize characteristics of published CRT in the field of healthcare epidemiology.
A systematic review was conducted to identify CRT with infection control outcomes.
We identified the following 7 epidemiological principles: (1) identify design type and justify the use of CRT; (2) account for clustering when estimating sample size and report intraclass correlation coefficient (ICC)/coefficient of variation (CV); (3) obtain consent; (4) define level of inference; (5) consider matching and/or stratification; (6) minimize bias and/or contamination; and (7) account for clustering in the analysis. Among 44 included studies, the most common design was CRT with crossover (n = 15, 34%), followed by parallel CRT (n = 11, 25%) and stratified CRT (n = 7, 16%). Moreover, 22 studies (50%) offered justification for their use of CRT, and 20 studies (45%) demonstrated that they accounted for clustering at the design phase. Only 15 studies (34%) reported the ICC, CV, or design effect. Also, 15 studies (34%) obtained waivers of consent, and 7 (16%) sought consent at the cluster level. Only 17 studies (39%) matched or stratified at randomization, and 10 studies (23%) did not report efforts to mitigate bias and/or contamination. Finally, 29 studies (88%) accounted for clustering in their analyses.
We must continue to improve the design and reporting of CRT to better evaluate the effectiveness of infection control interventions in the healthcare setting.
Prevalence of multidrug-resistant microorganisms (MDROs) continues to increase, while infection control gaps in healthcare settings facilitate their transmission between patients. In this setting, 5 distinct yet interlinked pathways are responsible for transmission. The complete transmission process is still not well understood. Designing and conducting a single research study capable of investigating all 5 complex and multifaceted pathways of hospital transmission would be costly and logistically burdensome. Therefore, this scoping review aims to synthesize the highest-quality published literature describing each of the 5 individual potential transmission pathways of MDROs in the healthcare setting and their overall contribution to patient-to-patient transmission.
In 3 databases, we performed 2 separate systematic searches for original research published during the last decade. The first search focused on MDRO transmission via the HCW or the environment to identify publications studying 5 specific transmission pathways: (1) patient to HCW, (2) patient to environment, (3) HCW to patient, (4) environment to patient, and (5) environment to HCW. The second search focused on overall patient-to-patient transmission regardless of the transmission pathway. Both searches were limited to transmission of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, multidrug-resistant A. baumannii, and carbapenem-resistant Enterobacteriaceae. After abstract screening of 5,026 manuscripts, researchers independently reviewed and rated the remaining papers using objective predefined criteria to identify the highest quality and most influential manuscripts.
High-quality manuscripts were identified for all 5 routes of transmission. Findings from these studies were consistent for all pathways; however, results describing the routes from the environment/HCW to a noncolonized patient were more limited and variable. Additionally, most research focused on MRSA, instead of other MDROs. The second search yielded 10 manuscripts (8 cohort studies) that demonstrated the overall contribution of patient-to-patient transmission in hospitals regardless of the transmission route. For MRSA, the reported cross-transmission was as high as 40%.
This scoping review brings together evidence supporting all 5 possible transmission pathways and illustrates the complex nature of patient-to-patient transmission of MDROs in hospitals. Our findings also confirm that transmission of MDROs in hospitals occurs frequently, suggesting that ongoing efforts are necessary to strengthen infection prevention and control to prevent the spread of MDROs.
A systematic review of quasi-experimental studies in the field of infectious diseases was published in 2005. The aim of this study was to assess improvements in the design and reporting of quasi-experiments 10 years after the initial review. We also aimed to report the statistical methods used to analyze quasi-experimental data.
Systematic review of articles published from January 1, 2013, to December 31, 2014, in 4 major infectious disease journals.
Quasi-experimental studies focused on infection control and antibiotic resistance were identified and classified based on 4 criteria: (1) type of quasi-experimental design used, (2) justification of the use of the design, (3) use of correct nomenclature to describe the design, and (4) statistical methods used.
Of 2,600 articles, 173 (7%) featured a quasi-experimental design, compared to 73 of 2,320 articles (3%) in the previous review (P<.01). Moreover, 21 articles (12%) utilized a study design with a control group; 6 (3.5%) justified the use of a quasi-experimental design; and 68 (39%) identified their design using the correct nomenclature. In addition, 2-group statistical tests were used in 75 studies (43%); 58 studies (34%) used standard regression analysis; 18 (10%) used segmented regression analysis; 7 (4%) used standard time-series analysis; 5 (3%) used segmented time-series analysis; and 10 (6%) did not utilize statistical methods for comparisons.
While some progress occurred over the decade, it is crucial to continue improving the design and reporting of quasi-experimental studies in the fields of infection control and antibiotic resistance to better evaluate the effectiveness of important interventions.
We assessed various locations and frequency of environmental sampling to maximize information and maintain efficiency when sampling for Acinetobacter baumannii. Although sampling sites in closer proximity to the patient were more likely positive, to fully capture environmental contamination, we found value in sampling all sites and across multiple days.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
Whether healthcare-associated infection data should be presented using indirect (current CMS/CDC methodology) or direct standardization remains controversial. We applied both methods to central-line–associated bloodstream infection data from 45 acute-care hospitals in Maryland from 2012 to 2014. We found that the 2 methods generate different hospital rankings with payment implications.
Quality measures are increasingly reported by hospitals to the Centers for Medicare and Medicaid Services (CMS), yet there may be tradeoffs in performance between infection control (IC) and other quality measures. Hospitals that performed best on IC measures did not perform well on most CMS non–IC quality measures.
Oropharyngeal cancer is increasing in prevalence in the UK and this is thought to be due to the emergence of disease related to human papilloma virus.
A literature review was conducted on the diagnosis and latest management of oropharyngeal cancer.
In non-smokers, human papilloma virus related disease is thought to have better outcomes, but this casts doubt on previous research which did not stratify patients according to human papilloma virus status. However, this theory provides a route for researchers to risk stratify and de-escalate treatments, and hence reduce treatment burden. In addition, the emergence of minimally invasive transoral techniques allows surgeons to remove large tumours without many of the side effects associated with radical (chemo)radiotherapy.
The emergence of human papilloma virus related disease and minimally invasive techniques have led the clinical and academic community to reconsider how oropharyngeal cancer is managed. Comparative and risk-stratification trials are urgently required and ongoing.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.