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Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.
Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.
Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.
The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.
To compare the effects of empiric carbapenems versus cycling cefepime and piperacillin/tazobactam on the rates of vancomycin-resistant Enterococcus (VRE) colonization, bloodstream infections, and outcomes of patients admitted with acute leukemia.
Retrospective clinical study with VRE molecular strain typing and gastrointestinal microbiome comparison.
A regional referral center for acute leukemia.
342 consecutive patients admitted with newly diagnosed acute leukemia.
In September 2015, we changed our empiric antibiotic of choice for neutropenic fever from a carbapenem to the cycling regimen. We studied 214 consecutive patients during the carbapenem period and 128 during the cycling period. Surveillance for VRE stool colonization was conducted weekly. Representative stool samples were analyzed for VRE MLST types and changes in the composition and diversity of the fecal microbiota.
The change in empiric antibiotics was associated with a significant decrease in VRE colonization (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.27–0.66), a switch in the dominant VRE MLST types on the unit, and some modifications in the gastrointestinal microbiome. There were no differences in total gram-positive or gram-negative BSIs. During the carbapenem period, we observed higher absolute numbers of Candida spp and fewer ESBL BSIs, but these did not reach statistical significance. Patients during the carbapenem period had longer lengths of stay and durations of severe neutropenia and 10% higher hospital cost.
Carbapenem-sparing empiric antibiotic regimens may have advantages related to VRE ecology, gastrointestinal dysbiosis, duration of neutropenia, cost and length of stay.
Optical parametric chirped-pulse amplification (OPCPA) [Dubietis et al., Opt. Commun. 88, 437 (1992)] implemented by multikilojoule Nd:glass pump lasers is a promising approach to produce ultraintense pulses (
). Technologies are being developed to upgrade the OMEGA EP Laser System with the goal to pump an optical parametric amplifier line (EP OPAL) with two of the OMEGA EP beamlines. The resulting ultraintense pulses (1.5 kJ, 20 fs,
) would be used jointly with picosecond and nanosecond pulses produced by the other two beamlines. A midscale OPAL pumped by the Multi-Terawatt (MTW) laser is being constructed to produce 7.5-J, 15-fs pulses and demonstrate scalable technologies suitable for the upgrade. MTW OPAL will share a target area with the MTW laser (50 J, 1 to 100 ps), enabling several joint-shot configurations. We report on the status of the MTW OPAL system, and the technology development required for this class of all-OPCPA laser system for ultraintense pulses.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
An effective method for enhancing milk production efficiency in dairy cows is to increase milk yield and significant progress has been achieved through intense selection, assisted by the application of new reproductive techniques. However this increased milk yield has been accompanied by a slow but steady decline in dairy cow fertility. The two main reasons for this reducing level of fertility appear to be selection for increased milk yield and large herd sizes, although the affect of the introduction of Holstein genes needs to be investigated. In addition, other negative consequences such as an increase in the incidence of metabolic diseases and lameness have been observed. This has given rise to public concern that the high-yielding dairy cow may be under a state of metabolic stress during peak lactation and therefore the welfare and performance of other body functions are compromised.
The reason for this decline in fertility is not well understood, although a nutritional influence on the initiation of oestrous cycles, follicular growth, oocyte quality and early embryonic development has been implicated. In early lactation dietary intake is unable to meet the demands of milk production and most cows enter a period of negative energy balance. Negative energy balance has a broadly similar effect to undernutrition leading to a mobilization of body reserves. Furthermore diets high in rumen degradable protein lead to an excess of rumen ammonia, which before it is converted to urea by the liver and excreted in the urine, may cause an alteration in the reproductive tract environment reducing embryo survival. Such major changes in the metabolic and endocrine systems can therefore influence fertility at a number of key points.
Possible reproductive sites where inadequate nutrition may have detrimental effects include: (i) the hypothalamic/pituitary gland where gonadotropin release may be impaired; (ii) a direct effect on the ovaries, where both follicular growth patterns and corpus luteum function may be directly influenced; (iii) the quality of the oocyte prior to ovulation may be reduced and coupled with an inadequate uterine environment will result in reduced embryo survival and (iv) there may be effects on subsequent embryo development. The initiation of normal oestrous cycles post partum is usually delayed in dairy cows with a higher genetic merit for milk production, confirming that intense selection towards high milk yield can compromise reproductive function. In addition, the effects of increased milk yield may include changes in circulating GH and insulin concentrations, which in turn alter both insulin-like growth factor (IGF) and IGF binding protein production. Nutrition has recently been shown to have a direct effect at the level of both the ovaries and the uterus to alter the expression of these growth factors.
In conclusion, further knowledge is required to determine how the metabolic changes associated with high milk output reduce fertility. Identification and understanding of the mechanisms involved and the key sites of action responsible for compromised reproductive function, will enable the identification of possible indices for future multiple-trait selection programmes.
While a direct relation between hospital construction and concomitant infection rates has been clearly established, few data are available regarding the environmental decontamination effects of renovation in which surfaces are replaced and regarding subsequent infection incidence.
Retrospective clinical study with vancomycin-resistant Enterococcus (VRE) molecular strain typing and environmental cultures.
A regional referral center for acute leukemia and hematopoietic stem-cell transplantation.
Overall, 536 consecutive hospital admissions for newly diagnosed acute leukemia or a first autologous or allogeneic stem-cell transplantation were reviewed.
During 2009–2010, our unit underwent complete remodeling including replacement of all surfaces. We assessed the effects of this construction on the incidence of hospital-acquired VRE colonization before, during, and after the renovation.
We observed a sharp decrease in VRE colonization rates (hazard ratio, <0.23; 95% confidence interval, 0.18–0.44; P<.0001) during the first year after the renovation, with a return to near baseline rates thereafter. The known risk factors for VRE colonization appeared to be stable over the study interval. Environmental cultures outside of patient rooms revealed several contaminated areas that are commonly touched by unit personnel. Multilocus sequence typing of VRE isolates that were cryopreserved over the study interval showed that dominant strains prior to construction disappeared and were replaced by other strains after the renovation.
Unit reconstruction interrupted endemic transmission of VRE, which resumed with novel strains upon reopening. Contamination of environmental surfaces and shared equipment may play an important role in endemic transmission of VRE.
Little is known about the precursors of suicide risk among primary-care patients. This study aimed to examine suicide risk in relation to patterns of clinical consultation, psychotropic drug prescribing, and psychiatric diagnoses.
Nested case-control study in the Clinical Practice Research Datalink (CPRD), England. Patients aged ⩾16 years who died by suicide during 2002–2011 (N = 2384) were matched on gender, age and practice with up to 20 living control patients (N = 46 899).
Risk was raised among non-consulting patients, and increased sharply with rising number of consultations in the preceding year [⩾12 consultations v. 1: unadjusted odds ratio (OR) 6.0, 95% confidence interval (CI) 4.9–7.3]. Markedly elevated risk was also associated with the prescribing of multiple psychotropic medication types (⩾5 types v. 0: OR 62.6, CI 44.3–88.4) and with having several psychiatric diagnoses (⩾4 diagnoses v. 0: OR 31.1, CI 19.3–50.1). Risk was also raised among patients living in more socially deprived localities. The confounding effect of multiple psychotropic drug types largely accounted for the rising risk gradient observed with increasing consultation frequency.
A greater proportion of patients with several psychiatric diagnoses, those prescribed multiple psychotropic medication types, and those who consult at very high frequency might be considered for referral to mental health services by their general practitioners. Non-consulters are also at increased risk, which suggests that conventional models of primary care may not be effective in meeting the needs of all people in the community experiencing major psychosocial difficulties.
Introduction / Innovation Concept: Adverse events due to medical error are a significant source of preventable morbidity and mortality in Canada’s emergency departments. Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) was introduced in 2006 as a strategy to minimize these errors. Although these strategies have been available and widely implemented in hospitals over the last decade, the optimal method of teaching these tools and strategies has not been elucidated. Methods: We endeavoured to introduce a twelve month longitudinal TeamSTEPPS program to physicians, nurses, and allied health care professionals in a busy tertiary care hospital via a multi-pronged approach consisting of group huddles, props in the department, and several social media strategies. Dedicated observers in the emergency department recorded the use of the strategies by staff members to identify improved and sustained use of TeamSTEPPS behaviours after they were introduced. Curriculum, Tool, or Material: The program that consists of five modules to improve patient safety outcomes: Team structure; Leadership; Situation Monitoring; Mutual support; and Communication. Each module consisted of educational tools including posters in the department explaining the concepts, twice weekly department huddles to discuss the importance of the monthly topic and promote team sharing with real life examples, as well as stimulating and generating discussions around the monthly theme on social media (Facebook, Twitter, and an on-line blog). For several modules, extra prompts, such as I PASS the BATON handover cards were also provided to act as reminder visual cues. The first two modules were rolled out with on-line music videos rewritten to promote the significance of the modules. A team performance observation tool was adopted from the TeamSTEPPS program, and behaviors were evaluated and recorded under the five domains. Conclusion: Although unable to detect a meaningful difference in our pre and post-implementation observations, we present a novel approach to educating a multi-disciplinary team about TeamSTEPPS in a busy emergency department, along with the challenges encountered in this unique area of research, and recommendations for further study to interested parties. The TeamSTEPPS program likely could offer as much to the emergency department as similar programs have to the aviation industry yet it requires extensive investigation within this health care venue.
We present new beryllium abundances for three unevolved stars with [Fe/H] in the range −0.4 to −1.6. The Be II doublet is detected in the three stars. A spectral synthesis analysis has been conducted to derive the abundances. We briefly discuss their Be and Li abundances, together with a wide sample of stars from the literature, in the context of mixing processes below the convection zone.
Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995–2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.
Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study.
One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials).
Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = −0.28, p = 0.007).
Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
The UK has seen a significant transition from Defined Benefit (“DB”) to Defined Contribution (“DC”) for occupational pension saving. The planned automatic enrolment program starting in 2012 is expected to increase the use of DC. The main features of DC are that investment risk falls onto the individual during the pre-retirement phase and that there are no guarantees as to investment returns or the level of pension. In July 2012, Steve Webb, the Pensions Minister, challenged industry to think hard about meeting the need for more certainty about pension savings in DC plans and to consider providing an affordable ‘Money Safe’ guarantee where the member would get back at least the nominal value of their contributions (individual, employer and tax relief). This paper explores whether this is viable for the mass market.
Molecular Dynamics (MD) and Metropolis Monte-Carlo (MMC) models of monomer B and decaborane implantation into Si and following rapid thermal annealing (RTA) processes have been developed in this paper. The implanted B dopant diffusion coefficients were obtained for different substrate temperatures. The simulation of decaborane ion implantation has revealed the formation of an amorphized area in a subsurface region, much larger than that of a single B+ implantation, with the same energy per ion. The B diffusion coefficient shows an unusual temperature dependence with two different activation energies. Low activation energy, less than 0.2, was obtained for a low-temperature region, and a higher activation energy, ˜ 3 ev, for a higher-temperature region which is typical for the RTA processing. The higher activation energy is comparable with the equilibrium activation energy, 3.4 ev, for B diffusion in Si.
We investigated spatial non-uniformity and optical anisotropy in hydrogenated silicon thin films using infrared spectroscopy and other techniques. The films ranged in morphology from amorphous to micro-crystalline, as determined by Raman spectroscopy and X-ray diffraction (XRD). Trace element analysis of the films was carried out using secondary ion mass spectrometry (SIMS). We used polarized attenuated total reflection (ATR) measurements together with Fourier transform infrared (FTIR) spectroscopy to investigate anisotropy in the Si-H covalent bonding structure of the films, and also to detect oxide impurity phases present at certain sites in some samples. The FTIR-ATR measurements were performed using a germanium (Ge) contact microprobe with a 100-micron sampling area, as well as on films deposited on standard crystalline Si and Ge ATR substrates. The Ge contact ATR microprobe enabled relatively interference-free measurements of the IR spectra of a-Si:H and µc-Si:H films deposited on conductive substrates such as stainless steel and transparent conductive oxides, and is also sensitive to the spatial distribution of oxide precipitates in the films. This measurement is difficult or impossible using transmission or reflection IR spectroscopy.