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An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.
Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).
BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). The change in KynA/QA was nominally associated with the magnitude of change in PROMIS-D scores (p = 0.074, Cohen's f2 = 0.054). Baseline KynA/QA did not predict response to BA therapy.
The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
No standardized surveillance criteria exist for surgical site infection after breast tissue expander (BTE) access. This report provides a framework for defining postaccess BTE infections and identifies contributing factors to infection during the expansion period. Implementing infection prevention guidelines for BTE access may reduce postaccess BTE infections.
We compared the fluorescent gel removal rate using fewer high-touch surfaces (HTSs) and rooms and determined the optimum number of HTSs and rooms needed to ensure accuracy using 2,942 HTSs in 228 rooms on 13 units. Randomly selecting 3 HTS in 2 rooms predicted the optimal removal rate.
In this systematic evaluation of fluorescent gel markers (FGM) applied to high-touch surfaces with a metered applicator (MA) made for the purpose versus a generic cotton swab (CS), removal rates were 60.5% (476 of 787) for the MA and 64.3% (506 of 787) for the CS. MA-FGM removal interpretation was more consistent, 83% versus 50% not removed, possibly due to less varied application and more adhesive gel.
Introduction: Hospitalization due to ambulatory care sensitive conditions (ACSC) is a proxy measure for access to primary care. Emergency medical services (EMS) are increasingly called when primary care cannot be accessed. A novel paramedic-nurse EMS Mobile Care Team (MCT) was implemented in an under-serviced community. The MCT responds in a non-transport unit to bookings from EMS, emergency and primary care and to low-acuity 911 calls in a defined geographic region. Our objective was to compare the prevalence of ACSC in ground ambulance (GA) responses before and after the introduction of the MCT. Methods: A cross-sectional analysis of GA and MCT patients with ACSC (determined by chief complaint, clinical impression, treatment protocol and medical history) one year pre- and one year post-MCT implementation was conducted for the period Oct. 1, 2012 to Sept. 30, 2014. Demographics were described. Predictors of ACSC were identified via logistic regression. Prevalence was compared with chi-squared analysis. Results: There were 975 calls pre- and 1208 GA/95 MCT calls post-MCT. ACSC in GA patients pre- and post-MCT was similar: n=122, 12.5% vs. n=185, 15.3%; p=0.06. ACSC in patients seen by EMS (GA plus MCT) increased in the post-period: 122 (12.5%) vs. 204 (15.7%) p=0.04. Pre vs post, GA calls differed by sex (p=0.007) but not age (65.38 ± 15.12 vs. 62.51 ± 20.48; p=0.16). Post-MCT, prevalence of specific ACSC increased for GA: hypertension (p<0.001) and congestive heart failure (p=0.04). MCT patients with ACSC were less likely to have a primary care provider compared to GA (90.2% and 87.6% vs. 63.2%; p=0.003, p=0.004). Conclusion: The prevalence of ACSC did not decrease for GA with the introduction of the MCT, but ACSC in the overall patient population served by EMS increased. It is possible more patients with ACSC call or are referred to EMS for the new MCT service. Given that MCT patients were less likely to have a primary care provider this may represent an increase in access to care, or a shift away from other emergency/episodic care. These associations must be further studied to inform the ideal utility of adding such services to EMS and healthcare systems.
We describe two cases of infant botulism due to Clostridium butyricum producing botulinum type E neurotoxin (BoNT/E) and a previously unreported environmental source. The infants presented at age 11 days with poor feeding and lethargy, hypotonia, dilated pupils and absent reflexes. Faecal samples were positive for C. butyricum BoNT/E. The infants recovered after treatment including botulism immune globulin intravenous (BIG-IV). C. butyricum BoNT/E was isolated from water from tanks housing pet ‘yellow-bellied’ terrapins (Trachemys scripta scripta): in case A the terrapins were in the infant's home; in case B a relative fed the terrapin prior to holding and feeding the infant when both visited another relative. C. butyricum isolates from the infants and the respective terrapin tank waters were indistinguishable by molecular typing. Review of a case of C. butyricum BoNT/E botulism in the UK found that there was a pet terrapin where the infant was living. It is concluded that the C. butyricum-producing BoNT type E in these cases of infant botulism most likely originated from pet terrapins. These findings reinforce public health advice that reptiles, including terrapins, are not suitable pets for children aged <5 years, and highlight the importance of hand washing after handling these pets.
To describe a pseudo-outbreak associated with loose bronchoscope biopsy ports caused by inadequate bronchoscope repair practices by third-party vendors and to alert healthcare personnel to assess bronchoscope repair practices.
A 925-bed tertiary care hospital in Baltimore, Maryland.
Patients who underwent bronchoscopy with certain bronchoscopes after they had been repaired by a third-party vendor.
An epidemiologic investigation was conducted to determine the cause of Pseudomonas putida growth in 4 bronchoalveolar lavage (BAL) specimens within a 3-day period in May 2008. All bronchoscopes were inspected, and cultures were obtained from bronchoscopes and the environment. Bronchoscope cleaning and maintenance practices were reviewed. Microbiologic results from BAL specimens and medical records were reviewed to find additional cases.
All 4 case patients had undergone bronchoscopy with one of 2 bronchoscopes, both of which had loose biopsy ports. Bronchoscope cultures grew P. putida, Pseudomonas aeruginosa, and Stenotrophomonas. The P. putida strains from the bronchoscopes matched those from the patients. Specimens from 12 additional patients who underwent bronchoscopy with these bronchoscopes grew P. putida, P. aeruginosa, or Stenotrophomonas. No patients developed clinical signs or symptoms of infection, but 7 were treated with antibiotics. Investigation revealed that the implicated bronchoscopes had been sent to an external vendor for repair; examination by the manufacturer revealed irregularities in repairs and nonstandard part replacements.
Third-party vendors without access to proprietary information may contribute to mechanical malfunction of medical devices, which can lead to contamination and incomplete disinfection.
The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2–5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5–5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.
Attempts were made to isolate viruses from babies' stools that contained adenoviruses detected by electron microscopy. One hundred and fifty-nine specimens from 71 children were studied and adenoviruses of established serotypes were isolated from 81 stools. Serial stool samples containing adenovirus particles were obtained from 35 children, and prolonged shedding of recognized serotypes was common. Simultaneous and sequential infections by different serotypes were also observed. Thirty-six children shed adenoviruses that could not be isolated using cell cultures normally used to detect adenoviruses, and nine of these children also shed adenoviruses of established serotypes. Passage in Chang conjunctival cell cultures allowed characterization of fastidious adenoviruses from 14 children as members of a previously unrecognized serotype.
Cryptosporidium species have emerged as a major cause of outbreaks of diarrhoea and have been associated with consumption of contaminated recreational and drinking water and food as well as contact with infected attendees of child-care programmes. In August 2007, the Colorado Department of Public Health and Environment detected an increase in cryptosporidiosis cases over baseline values. We conducted a case-control study to assess risk factors for infection and collected stool specimens from ill persons for microscopy and molecular analysis. Laboratory-confirmed cases (n=47) were more likely to have swallowed untreated water from a lake, river, or stream [adjusted matched odds ratio (aOR) 8·0, 95% confidence interval (CI) 1·3–48·1], have had exposure to recreational water (aOR 4·6, 95% CI 1·4–14·6), or have had contact with a child in a child-care programme or in diapers (aOR 3·8, 95% CI 1·5–9·6). Although exposure to recreational water is commonly implicated in summertime cryptosporidiosis outbreaks, this study demonstrates that investigations of increased incidence of cases in summer should also examine other potential risk factors. This study emphasizes the need for public health education efforts that address the multiple transmission routes for Cryptosporidium and appropriate prevention measures to avoid future transmission.
The stools of 37 newborn babies born in hospital were examined for the presence of virus. An extract of every stool passed by each baby was examined in the electron microscope and inoculated into cell cultures. The babies were delivered in four separate maternity units (A–D). All the babies from units A and C (9 babies) were found to be excreting rotavirus though none showed any evidence of diarrhoea. Two of the babies also excreted astrovirus. Subsequently unit A was closed for cleaning and, on reopening with more restrictions on visitors, a further 19 babies were examined. No virus was found in any of their stools, nor was virus observed in the stools of babies from units B and D, where visiting was also more restricted. Visiting restrictions in these units excluded older siblings of the babies. No virus was cultured from any stools in this study.
Twenty-seven babies from one deprived housing area in Glasgow were followed-up regularly, for periods varying between 2 months and 11 months (mean 7 months), in a prospective study of the viruses to be found in their stools by electron microscopy. Weekly stool specimens were collected in the home together with a history of the baby's health. Additional stool specimens were obtained, up to a maximum of one per day, during admissions to hospital. Over 500 specimens were obtained at home and another 320 in hospital. A wide variety of viruses (over 200 recognizates) were detected and it has been possible to plot their temporal relation to disease episodes. It became apparent that virus excretion was frequently unaccompanied by evidence of illness and it has not been possible to describe a typical illness syndrome associated with any of the morphological types of virus observed.
The results suggest that, in one area of Glasgow at least, patterns of virus excretion in young babies are complex and will need further elucidation before the need for a vaccine to prevent infantile diarrhoea could be defined.
Stools from 183 babies under 2 years of age admitted to Ruchill Hospital with diarrhoea were examined by electron microscopy, virus culture, bacterial culture and light microscopy. As far as possible, several stools were examined from each patient and the results showed rotaviruses, astroviruses and other viruses in association with symptoms, as well as the expected bacterial pathogens. Examination of several stools from the same patient also showed that in this age group the viral flora of the gut changes rapidly and that the viruses seen by electron microscopy were only rarely grown in cell culture and vice versa. This phenomenon was particularly noted with adenoviruses. In 30% of cases no microbial pathogen was identified and in the remainder the presence of the infecting organism did not always coincide with the symptoms. It is concluded that, with viruses at least, presence of the organism does not constitute proof of causation.
We describe the epidemiology of Staphylococcus aureus colonization among 200 healthcare workers. The prevalence of S. aureus was 28%, and the prevalence of methicillin-resistant S. aureus (MRSA) was 2%. The incidence of MRSA colonization was extremely low. This study suggests that the risk of MRSA transmission to healthcare workers is low in a hospital where MRSA is endemic.
We describe an investigation of soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains in 2 healthcare workers employed in an outpatient clinic for patients with human immunodeficiency virus infection. Cultures of environmental samples from multiple surfaces in the clinic grew toxin-producing CA-MRSA strains, suggesting fomites may play a role in the transmission of these strains of MRSA.
Alternate 2·4 m wide strips of a mixture of birdsfoot trefoil (Lotus corniculatus L.) with white clover (Trifolium repens L.) (BW), and of red clover (Trifolium pratense L.) (RC) were offered in the proportions (by area) of 0·80[ratio ]0·20, 0·67[ratio ]0·33, 0·33[ratio ]0·67 and 0·20[ratio ]0·80 to yearling heifers in groups of three for periods of 3 days over four replicates in time, balanced for effects of previous treatments. Observations on the distribution of grazing activity and biting rate were made over 3 h periods each evening, and on the morning of Day 2. Biting rates were consistently higher on BW than RC (52·3 v. 46·3±0·59 bites/min, P<0·001). Initially the animals showed a strong tendency to concentrate grazing on the sward of smaller proportional area, but the selection coefficient (log θ) changed from positive to negative with time as herbage on minority strips was depleted. These results are discussed in the context of concepts of partial grazing preference.
The effects of manipulation of sward maturity on ingestive behaviour and diet selection of grazing cattle were tested in two experiments using legumes which are equally preferred by cattle. Yearling heifers, in groups of three, grazed plots formed by alternate 2·4 m wide strips of a mixture of birdsfoot trefoil (Lotus corniculatus L.) and white clover (Trifolium repens L.) (BW) and strips of red clover (Trifolium pratense L.) (RC). The treatments comprised four combinations of each of the two swards at two contrasting levels of maturity/height replicated over four successive 3-day periods, in an order which balanced the effect of previous treatments. Observations of the distribution of grazing activity and biting rate were made over 3-hour periods each evening and in the morning of Day 2.
Rate of biting was generally greater on immature than mature swards, and on BW than on RC, with little evidence of interactions between these effects. The animals demonstrated partial preference throughout the two studies, the proportion of grazing time devoted to BW being 0·40±0·010 in Expt 1 and 0·47±0·017 in Expt 2. The distribution of grazing time between sward type and maturity combinations was influenced progressively by herbage mass and height contrasts as strips were grazed down. An overall analysis using the results from these studies and a companion experiment indicated differences between studies in partial preference for BW and RC which appeared to be related to variations in sward morphology.
Little is understood about the evolution of structural and functional brain changes during the course of uncontrolled focal status epilepticus in humans.
We serially evaluated and treated a nine-year-old girl with refractory focal status epilepticus. Long-term EEG monitoring, MRI, MRA, SPECT, intraoperative visualization of affected cortex, and neuropathological examination of a biopsy specimen were conducted over a three year time span. Imaging changes were correlated with simultaneous treatment and EEG findings.
The EEG monitoring showed almost continuous spike discharges emanating initially from the right frontocentral area. These EEG abnormalities were intermittently suppressed by treatment with anesthetics. Over time, additional brain areas developed epileptiform EEG abnormalities. Serial MRI studies demonstrated an evolution of changes from normal, through increased regional T2 signal to generalized atrophy. An MRAdemonstrated dilatation of the middle cerebral artery stem on the right compared to the left with a broad distribution of flow-related enhancement. An 18FDG-PET scan showed a dramatically abnormal metabolic profile in the same right frontocentral areas, which modulated in response to treatment during the course of the illness. A right frontotemporal craniotomy revealed a markedly hyperemic cortical focus including vascular shunting. A sample of resected cortex showed severe gliosis and neuronal death.
The co-registration of structural and functional imaging and its correlation with operative and pathological findings in this case illustrates the relentless progression of regional and generalized abnormalities in intractable focal status epilepticus that were only transiently modified by exhaustive therapeutic interventions. Increased flow through large vessels appeared to be shunted and did not translate into increased microvascular perfusion.
The development of intensity modulated radiotherapy (IMRT) has allowed the delivery of concave dose distributions. Planning studies have demonstrated the potential clinical benefit of IMRT in the treatment of the prostate and pelvic nodes in patients with advanced prostate cancer. As a consequence, IMRT was clinically implemented in the Royal Marsden NHS Trust in September 2000, using Elekta Sli series linear accelerators and NOMOS Corvus v3.0 planning system. As a relatively new treatment procedure in the United Kingdom, the clinical implementation involved developing appropriate quality assurance and verification procedures as well as training staff. This paper describes the practicalities of implementing IMRT into the routine workload of the radiotherapy department.