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To estimate the health-related quality of life (HRQOL) and impact of concurrent pain on HRQOL in patients seeking treatment for depression in a 6 month observational study in the United Kingdom (subsample results from pan-European study).
HRQOL was measured using two generic quality of life instruments: the Short Form 36 Health Status Survey (SF-36) and the EuroQol (EQ-5D). Pain was assessed using a visual analogue scale (range 0-100, no/mild pain [NMP] 0-29, clinically significant pain ≥30).
608 eligible patients were enrolled, mean age 42.8 years (SD 14.7) and 61.2% were female. 49.4% of patients reported NMP; 10.8% had significant pain from a co-morbid medical condition known to cause pain (PMC) and 39.8% had significant pain associated with a medical disorder not known to cause pain or without further co-morbidity (PD). SF-36 physical component scores were lowest in the PMC group, 36.7 (SD 9.7); with improving scores in the PD group, 44.4 (SD 10.0) and the NMP group, 54.5 (SD 8.3). There was no marked variation in mental component summary scores between the groups; 23.0 (SD 8.5), 20.4 (SD 9.1) and 21.7 (SD 10.8) respectively. A similar trend in HRQOL loss was observed for the EQ-5D health state index, where scores of 0.30 (SD 0.32), 0.41 (SD 0.30) and 0.60 (SD 0.25) were observed respectively.
A high proportion of patients presented with pain presumably related to depression. The presence of concurrent pain appears to be associated with reductions in SF-36 physical component scores and overall HRQOL (EQ-5D).
Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.
The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.
There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.
Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
We present observations of 50 deg2 of the Mopra carbon monoxide (CO) survey of the Southern Galactic Plane, covering Galactic longitudes l = 300–350° and latitudes |b| ⩽ 0.5°. These data have been taken at 0.6 arcmin spatial resolution and 0.1 km s−1spectral resolution, providing an unprecedented view of the molecular clouds and gas of the Southern Galactic Plane in the 109–115 GHz J = 1–0 transitions of 12CO, 13CO, C18O, and C17O.
We present a series of velocity-integrated maps, spectra, and position-velocity plots that illustrate Galactic arm structures and trace masses on the order of ~106 M⊙ deg−2, and include a preliminary catalogue of C18O clumps located between l = 330–340°. Together with the information about the noise statistics of the survey, these data can be retrieved from the Mopra CO website and the PASA data store.
The main goal of this paper is to provide insights into swash flow dynamics, generated by a non-breaking solitary wave on a steep slope. Both laboratory experiments and numerical simulations are conducted to investigate the details of runup and rundown processes. Special attention is given to the evolution of the bottom boundary layer over the slope in terms of flow separation, vortex formation and the development of a hydraulic jump during the rundown phase. Laboratory experiments were performed to measure the flow velocity fields by means of high-speed particle image velocimetry (HSPIV). Detailed pathline patterns of the swash flows and free-surface profiles were also visualized. Highly resolved computational fluid dynamics (CFD) simulations were carried out. Numerical results are compared with laboratory measurements with a focus on the velocities inside the boundary layer. The overall agreement is excellent during the initial stage of the runup process. However, discrepancies in the model/data comparison grow as time advances because the numerical model does not simulate the shoreline dynamics accurately. Introducing small temporal and spatial shifts in the comparison yields adequate agreement during the entire rundown process. Highly resolved numerical solutions are used to study physical variables that are not measured in laboratory experiments (e.g. pressure field and bottom shear stress). It is shown that the main mechanism for vortex shedding is correlated with the large pressure gradient along the slope as the rundown flow transitions from supercritical to subcritical, under the developing hydraulic jump. Furthermore, the bottom shear stress analysis indicates that the largest values occur at the shoreline and that the relatively large bottom shear stress also takes place within the supercritical flow region, being associated with the backwash vortex system rather than the plunging wave. It is clearly demonstrated that the combination of laboratory observations and numerical simulations have indeed provided significant insights into the swash flow processes.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
Introduction: Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis, and 2) to assess its prognostic value in the management of renal colic (PROSPERO: 42016035331). Methods: An electronic database search of MEDLINE, EMBASE, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were CT evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by conference with a third reviewer.Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary outcome of prognostic value was reported as a narrative summary. Results: The electronic search yielded 627 unique titles. After relevance screening, 25 papers underwent full-text review, and 8 articles met all inclusion criteria. Of these, 5 high-quality studies (N=1773) were included in the meta-analysis for diagnostic accuracy, and three yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% CI=67.1% to 73.2%) and 75.4% (95% CI=72.5% to 78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect.Three studies examining prognostic value noted a higher likelihood of a large stone or surgical intervention with positive POCUS findings. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation. Conclusion: Point-of-care ultrasound is of modest accuracy for the diagnosis of nephrolithiasis. While positive POCUS findings are associated with larger stones and greater likelihood for intervention, the clinical importance of this is unclear.
Ultrasound (US) detects synovitis more accurately than clinical examination (CE) in people with rheumatoid arthritis (RA). This review aimed to investigate the use of US, compared to CE alone, in treatment strategies for RA, and to estimate its potential to be cost-effective in making treatment decisions.
A systematic review was conducted of studies: investigating RA treatment response or strategies that compared US with CE-assessed synovitis; and of tapering RA treatment (1). A model was constructed to investigate the potential cost-effectiveness of US in (i) selecting patients suitable for treatment tapering; and (ii) avoiding treatment escalation (2).
Seven prospective cohort studies suggested US-detected synovitis was significantly associated with a treatment response or tapering failure, whereas in most cases clinical examination alone was not. Two randomized controlled trials (RCTs) identified suggested that US added to the Disease Activity Index (DAS)-based treatment strategies but did not significantly improve primary outcomes, but was associated with improved rate of DAS remission. The evidence showed that some patients (proportions varied widely) who had achieved low disease activity could have treatment tapered, with no, or little, short-term harm to the patient.
The model estimated that an average reduction of 2.5 percent in the costs of biological disease-modifying anti-rheumatic drug (bDMARDs) was sufficient to cover the costs of performing US every three months. This value increased to 4 percent and 13 percent for the costs of conventional disease-modifying anti-rheumatic drug (cDMARDs) depending on the assumed regimen.
Use of US to monitor synovitis could potentially be a cost-effective approach, given that low proportions of patients for whom clinicians consider amending treatment, would need to taper treatment, or remain on therapy without escalation. US could provide clinicians with more confidence in reducing the drug burden. However, there is considerable uncertainty in this conclusion due to lack of robust data relating to key parameters.
To measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA).
Prospective cohort study from October 4, 2008, through December 3, 2012.
Seven acute care hospitals in or near Toronto, Canada.
Total of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts.
Baseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing.
Overall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002–.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001–.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households.
Household transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant.
Carbapenem-resistant Acinetobacter baumannii (CRAB) with diverse multilocus sequence typing emerged among our nursing home residents (6.5%) with a high background rate of MRSA (32.2%). Rectal swabs yielded a higher rate of CRAB detection than axillary or nasal swabs. Bed-bound status, use of adult diapers, and nasogastric tube were risk factors for CRAB colonization.
Flexible electronics has emerged as a very promising field, in particular,wearable, bendable, and stretchable strain sensors with high sensitivity which could be used for human motion detection, sports performance monitoring, etc. In this paper, a highly stretchable and sensitive strain sensor composed of reduced graphene oxide foam and elastomer composite is fabricated by assembly and followed by a polymer immersing process. The strain sensor has demonstrated high stretchability and sensitivity. Furthermore, the device was employed for gauging muscle-induced strain which results in high sensitivity and reproducibility. The developed strain sensors showed great application potential in fields of biomechanical systems.
The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6–75·5] and 68·9% (95% CrI 66·2–71·6), respectively. Risks of death were higher in the youngest (0–4 years) and oldest (⩾60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone.
Therapeutic nihilism on treating psychopathy is widespread and is largely based on many outdated and poorly designed studies. Important recent advances have been made in assessing psychopathy and recidivism risks, as well as in offender rehabilitation to reduce reoffending, all of which are now well supported by a considerable literature based on credible empirical research. A 2-component model to guide risk reduction treatment of psychopathy has been proposed based on the integration of key points from the 3 bodies of literature. Treatment programs in line with the model have been in operation, and the results of early outcome evaluations are encouraging. Important advances also have been made in understanding the possible etiology of mentally disordered offenders with schizophrenia and history of criminality and violence, some with significant features of psychopathy. This article presents a review of recent research on risk reduction treatment of psychopathy with the additional aim to extend the research to the treatment of mentally disordered offenders with schizophrenia, violence, and psychopathy.