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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.
There is limited evidence of the safety and impact of task-shared care for people with severe mental illnesses (SMI; psychotic disorders and bipolar disorder) in low-income countries. The aim of this study was to evaluate the safety and impact of a district-level plan for task-shared mental health care on 6 and 12-month clinical and social outcomes of people with SMI in rural southern Ethiopia.
In the Programme for Improving Mental health carE, we conducted an intervention cohort study. Trained primary healthcare (PHC) workers assessed community referrals, diagnosed SMI and initiated treatment, with independent research diagnostic assessments by psychiatric nurses. Primary outcomes were symptom severity and disability. Secondary outcomes included discrimination and restraint.
Almost all (94.5%) PHC worker diagnoses of SMI were verified by psychiatric nurses. All prescribing was within recommended dose limits. A total of 245 (81.7%) people with SMI were re-assessed at 12 months. Minimally adequate treatment was received by 29.8%. All clinical and social outcomes improved significantly. The impact on disability (standardised mean difference 0.50; 95% confidence interval (CI) 0.35–0.65) was greater than impact on symptom severity (standardised mean difference 0.28; 95% CI 0.13–0.44). Being restrained in the previous 12 months reduced from 25.3 to 10.6%, and discrimination scores reduced significantly.
An integrated district level mental health care plan employing task-sharing safely addressed the large treatment gap for people with SMI in a rural, low-income country setting. Randomised controlled trials of differing models of task-shared care for people with SMI are warranted.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
OBJECTIVES/SPECIFIC AIMS: Focal cartilage injuries of the knee joint are common and present a treatment challenge due to minimal intrinsic repair. Cartilage tissue engineering techniques currently used in clinical practice are expensive, cumbersome, and often ineffective in patients with mechanical or medical comorbidities. To address these issues, we developed an acellular nanofibrous scaffold with encapsulated growth factors designed to enhanced articular cartilage repair. Our goal is to evaluate this technology in vitro and pilot a large animal model for eventual translation into human subjects. METHODS/STUDY POPULATION: Hyaluronic acid (HA, 65 kDa) will be methacrylated (~40% modification, MeHA) and conjugated with cell-adhesive (RGD) groups. A solution of 4% wt/vol MeHA, 2% wt/vol polyethylene oxide (900 kDa), 0.05% wt/vol Irgacure 2959, and 0.005% wt/vol stromal cell-derived factor-1α (SDF-1α) and/or transforming growth factor-β3 (TGF-β3) will be prepared in ddH2O. The solution will be electrospun onto a rotating mandrel to achieve a dry scaffold thickness of 0.5 mm. The scaffold matt will be UV cross-linked and 5 mm-diameter samples will be cut out. Four groups of scaffolds will be prepared: MeHA, MeHA+SDF, MeHA+TGF, MeHA+SDF+TGF. All groups will be evaluated for fiber diameter, swell thickness, equilibrium compressive modulus, degradation rate, and growth factor release rate over 4 weeks (n=10). Scaffolds will also be seeded with juvenile porcine MSCs (5×104) in 200 μL of medium incubated for 24 hours. Seeded scaffolds will be evaluated for equilibrium compressive modulus, cell infiltration, and chondrogenesis at 4 and 8 weeks (n=10). Scaffolds will then be evaluated in a juvenile Yucatan minipig cartilage defect model. In total, 6 animals will undergo bilateral knee surgery to create four 4 mm-diameter full-thickness cartilage defects in each trochlear grove. All defects will receive microfracture to release marrow elements. Each knee will receive 2 scaffolds of the same group (replicates) with paired microfracture controls, resulting in a sample size of 3. Animals will be sacrificed at 12 weeks and defects will be evaluated via non-destructive indentation testing for mechanical properties, microCT for defect fill and subchondral bone morphology, and histology for ICRS II Visual Histological Assessment Scoring. RESULTS/ANTICIPATED RESULTS: Our preliminary studies have shown reliable replication of electrospun MeHA scaffolds. We anticipate cross-linking density to correlate positively with compressive modulus, and negatively with swell thickness, degradation rate, and growth factor release rate. We anticipate the addition of SDF-1α and TGF-β3 to increase cell infiltration and chondrogenesis, respectively, within seeded scaffolds. Similarly, we expect minipig defects treated with growth factor-releasing scaffolds to show greater mechanical properties, defect fill, and ICRS II score compared with MeHA scaffolds without growth factor. DISCUSSION/SIGNIFICANCE OF IMPACT: This study has the potential to show how an HA-based cell-free scaffold can be augmented with 2 growth factors that act synergistically to improve cartilage repair in a large animal model. This technology would improve upon the cell-free scaffolds already used clinically for autologous matrix-induced chondrogenesis and is directly translatable.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Osteoradionecrosis is a significant complication of head and neck cancer treatment, and its most severe form (grade III) necessitates radical surgery. This study aimed to compare the cost of free-flap reconstructive surgery for grade III osteoradionecrosis and similar non-osteoradionecrosis cases in order to assess the cost burden of osteoradionecrosis treatment.
All patients who underwent free-flap reconstructive surgery for osteoradionecrosis between July 2004 and July 2010 at Auckland City Hospital (19 patients) were identified, and relevant data were collected retrospectively. These patients were matched in terms of age and sex with patients who underwent free-flap reconstructive surgery.
The treatment cost was 44 per cent higher in osteoradionecrosis patients when compared to non-osteoradionecrosis patients.
The significant financial burden on the health system, and the growing evidence for the effectiveness of pentoxifylline, tocopherol and clodronate, should prompt us to explore this alternative treatment further.
Among dialysis facilities participating in a bloodstream infection (BSI) prevention collaborative, access-related BSI incidence rate improvements observed immediately following implementation of a bundle of BSI prevention interventions were sustained for up to 4 years. Overall, BSI incidence remained unchanged from baseline in the current analysis.
This paper objectively evaluates current information available to the general public related to glue ear on the World Wide Web.
The term ‘glue ear’ was typed into the 3 most frequently used internet search engines – Google, Bing and Yahoo – and the first 20 links were analysed. The first 400 words of each page were used to calculate the Flesch–Kincaid readability score. Each website was subsequently graded using the Discern instrument, which gauges quality and content of literature.
The websites Webmd.boots.com, Bupa.co.uk and Patient.co.uk received the highest overall scores. These reflected top scores in either readability or Discern instrument assessment, but not both. Readability and Discern scores increased with the presence of a marketing or advertising incentive. The Patient.co.uk website had the highest Discern score and third highest readability score.
There is huge variation in the quality of information available to patients on the internet. Some websites may be accessible to a wide range of reading ages but have poor quality content, and vice versa. Clinicians should be aware of indicators of quality, and use validated instruments to assess and recommend literature.
Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013–2014 influenza season. Little is known about the epidemiology of severe influenza during this season.
A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.
A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4–6.9], P=.006 and 50–64 years, 2.5 [1.3–4.9], P=.007; reference age 18–49 years), male sex (1.9 [1.1–3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9–37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2–1.4], P<.001).
Risk factors for death among US patients with severe influenza during the 2013–2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.
Infect. Control Hosp. Epidemiol. 2015;36(11):1251–1260
Investigation of an outbreak of Clostridium difficile infection (CDI) at a hemodialysis facility revealed evidence that limited intrafacility transmission occurred despite adherence to published infection control standards for dialysis clinics. Outpatient dialysis facilities should consider CDI prevention, including environmental disinfection for C. difficile, when formulating their infection control plans.
Infect. Control Hosp. Epidemiol. 2015;36(8):972–974
Glycolipid transfer proteins (GLTPs) originally were identified as small (~24 kDa), soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. GLTPs and related homologs now are known to adopt a unique, helically dominated, two-layer ‘sandwich’ architecture defined as the GLTP-fold that provides the structural underpinning for the eukaryotic GLTP superfamily. Recent advances now provide exquisite insights into structural features responsible for lipid headgroup selectivity as well as the adaptability of the hydrophobic compartment for accommodating hydrocarbon chains of differing length and unsaturation. A new understanding of the structural versatility and evolutionary premium placed on the GLTP motif has emerged. Human GLTP-motifs have evolved to function not only as glucosylceramide binding/transferring domains for phosphoinositol 4-phosphate adaptor protein-2 during glycosphingolipid biosynthesis but also as selective binding/transfer proteins for ceramide-1-phosphate. The latter, known as ceramide-1-phosphate transfer protein, recently has been shown to form GLTP-fold while critically regulating Group-IV cytoplasmic phospholipase A2 activity and pro-inflammatory eicosanoid production.
This study aimed (1) to report the long-term effects of infliximab, a murine monoclonal antibody directed against tumour necrosis factor-α, on autoimmune inner ear disease, and (2) to discuss dilemmas surrounding the long-term management of autoimmune inner ear disease.
A 49-year-old man presented with sudden-onset, left-sided, sensorineural hearing loss, tinnitus and vertigo. He was prescribed oral prednisolone, with benefit. Over several subsequent months, he experienced frequent relapses and progressive deterioration of high-frequency hearing bilaterally. Multiple agents failed to stabilise his condition. Following infliximab treatment, there was a documented and sustained improvement in his hearing and tinnitus. He stopped the treatment after 46 weeks, with rapid relapse of his condition. His hearing recovered quickly again after recommencing infliximab.
The benefits of prolonged infliximab use and potential side effects must be balanced against allowing the disease to take its course, with progressive deafness. Randomised controlled trials are required to assess infliximab's optimal duration of use, long-term efficacy and safety in the treatment of autoimmune inner ear disease.