Aims/hypothesis
The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes.
Methods
A sample of 302 diabetic patients aged ...≥70 years was assessed for dementia or cognitive impairment without dementia in 2001–2002 and a subsample of non-demented patients (
n
= 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH.
Results
There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06–8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43–12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline.
Conclusions/interpretation
Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.
SCUBA-2 is a 10 000-bolometer submillimetre camera on the James Clerk Maxwell Telescope. The instrument commissioning was completed in 2011 September, and full science operations began in 2011 ...October. To harness the full potential of this powerful new astronomical tool, the instrument calibration must be accurate and well understood. To this end, the algorithms for calculating the line-of-sight opacity have been improved, and the derived atmospheric extinction relationships at both wavebands of the SCUBA-2 instrument are presented. The results from over 500 primary and secondary calibrator observations have allowed accurate determination of the flux conversion factors (FCF) for the 850 and 450 μm arrays. Descriptions of the instrument beam shape and photometry methods are presented. The calibration factors are well determined, with relative calibration accuracy better than 5 per cent at 850 μm and 10 per cent at 450 μm, reflecting the success of the derived opacity relations as well as the stability of the performance of the instrument over several months. The sample size of the calibration observations and accurate FCFs have allowed the determination of the 850 and 450 μm fluxes of several well-known submillimetre sources, and these results are compared with previous measurements from SCUBA.
Summary Background Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this ...treatment combination provided greater survival benefit than did chlorambucil or fludarabine. Methods 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. Findings There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38% vs 15%, respectively; overall response rate 94% vs 80%, respectively; p<0·0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0·006 and 0·04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0·00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (VH ) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. Interpretation Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.
Summary Objective Clinical tools are needed to identify and target a neuropathic-like phenotype, which may be associated with central sensitization (CS), in osteoarthritis (OA). The modified ...painDETECT questionnaire (mPD-Q) has face and content validity for identifying neuropathic-like symptoms in knee OA. To further validate the mPD-Q, this study assessed the unknown relationship between mPD-Q scores and signs of CS on quantitative sensory testing (QST) in knee OA. Design 36 Individuals were recruited with chronic, symptomatic, knee OA without other pain/neurological conditions. Reference QST data were obtained from 18 controls/32 eligible knees, enabling identification of sensory abnormalities/CS among case knees. A standardized questionnaire assessed psychological factors (depressive symptoms and pain catastrophizing), and for individual knees, mPD-Q and pain intensity scores. A standardized/comprehensive QST protocol was conducted for each knee. QST signs of CS were defined as: mechanical hyperalgesia and/or enhanced temporal summation and/or allodynia. The relationship between the presence of CS (yes/no) and a pre-selected mPD-Q score (≤12 or >12), by knees, was assessed using generalized estimating equations. Results Among 57 eligible case knees, 45.6% had ≥1 sign of CS. Controlling for age, knees with higher mPD-Q scores (>12.0) had higher odds of having QST signs of CS (adjusted odds ratio (OR) = 5.6; 95% confidence interval (CI), 1.3–22.9). This relationship was unaffected by controlling for depression and pain intensity, but was attenuated by pain catastrophizing. Conclusions Among painful OA knees, higher mPD-Q scores were associated with greater odds of having signs of CS. Thus, the mPD-Q may aid the identification of CS in people with chronic knee OA.
Submillimetre Common-User Bolometer Array 2 (SCUBA-2) is an innovative 10 000 pixel bolometer camera operating at submillimetre wavelengths on the James Clerk Maxwell Telescope (JCMT). The camera has ...the capability to carry out wide-field surveys to unprecedented depths, addressing key questions relating to the origins of galaxies, stars and planets. With two imaging arrays working simultaneously in the atmospheric windows at 450 and 850 μm, the vast increase in pixel count means that SCUBA-2 maps the sky 100-150 times faster than the previous SCUBA instrument. In this paper, we present an overview of the instrument, discuss the physical characteristics of the superconducting detector arrays, outline the observing modes and data acquisition, and present the early performance figures on the telescope. We also showcase the capabilities of the instrument via some early examples of the science SCUBA-2 that have already been undertaken. In 2012 February, SCUBA-2 began a series of unique legacy surveys for the JCMT community. These surveys will take 2.5 yr and the results are already providing complementary data to the shorter wavelength, shallower, larger area surveys from Herschel. The SCUBA-2 surveys will also provide a wealth of information for further study with new facilities such as ALMA, and future telescopes such as CCAT and SPICA.
•Depressed mothers have higher self-directed expressed emotion.•Novel coding systems for EE toward self and mother developed and tested.•Criticism of mother mediates maternal depression to child ...negative affect.•Relational interventions can target maternal representations in depressed mothers.
Maternal depression is a widely recognized public health concern with significant implications for child functioning, including the development of negative child affect and risk for later depression. Negative mental representations may partially account for the association between maternal depression and child negative affect.
The effect of depression on low-income mothers’ representations of their child, self, and mother was assessed via Expressed Emotion (EE) during Five-Minute Speech Samples. Direct and indirect pathways between maternal depression, EE, and child negative affect were examined. Mothers (M = 24 years old) who had experienced a major depressive episode (n = 144) since child's birth, non-depressed comparison mothers (n = 62), and their children participated.
Examination of between-group differences revealed that depressed mothers had higher levels of overall self EE. Trend results also suggest depressed mothers may have higher overall EE toward their children and their own mothers. Novel coding systems for EE toward self (Identity and Depressotypic Cognitions) and EE toward mother (Source of Concrete Support and Resolution of Past Adversity) were also developed and tested. A significant indirect relation was found between maternal baseline depression and child negative affect at 26 months via the mother's level of EE-Criticism of her mother.
Certain EE subcodes may need to be adapted for young children and high-risk, low-income participants.
Findings highlights the importance of relational interventions that focus on maternal representations for women with depression and their children.
The ATLAS3D project is a multiwavelength survey combined with a theoretical modelling effort. The observations span from the radio to the millimetre and optical, and provide multicolour imaging, ...two-dimensional kinematics of the atomic (H i), molecular (CO) and ionized gas (Hβ, O iii and N i), together with the kinematics and population of the stars (Hβ, Fe5015 and Mg b), for a carefully selected, volume-limited (1.16 × 105 Mpc3) sample of 260 early-type (elliptical E and lenticular S0) galaxies (ETGs). The models include semi-analytic, N-body binary mergers and cosmological simulations of galaxy formation. Here we present the science goals for the project and introduce the galaxy sample and the selection criteria. The sample consists of nearby (D < 42 Mpc, |δ− 29°| < 35°, |b| > 15°) morphologically selected ETGs extracted from a parent sample of 871 galaxies (8 per cent E, 22 per cent S0 and 70 per cent spirals) brighter than MK
< −21.5 mag (stellar mass M
★≳ 6 ×109 M⊙). We analyse possible selection biases and we conclude that the parent sample is essentially complete and statistically representative of the nearby galaxy population. We present the size-luminosity relation for the spirals and ETGs and show that the ETGs in the ATLAS3D sample define a tight red sequence in a colour-magnitude diagram, with few objects in the transition from the blue cloud. We describe the strategy of the SAURON integral field observations and the extraction of the stellar kinematics with the ppxf method. We find typical 1σ errors of ΔV≈ 6 km s−1, Δσ≈ 7 km s−1, Δh
3≈Δh
4≈ 0.03 in the mean velocity, the velocity dispersion and Gauss-Hermite (GH) moments for galaxies with effective dispersion σe≳ 120 km s−1. For galaxies with lower σe (≈40 per cent of the sample) the GH moments are gradually penalized by ppxf towards zero to suppress the noise produced by the spectral undersampling and only V and σ can be measured. We give an overview of the characteristics of the other main data sets already available for our sample and of the ongoing modelling projects.
Context: There are limited published data characterizing severe hypoglycemia complicating type 2 diabetes.
Objective: The objective of the study was to determine the incidence and predictors of ...severe hypoglycemia in community-dwelling type 2 patients.
Design: This was a longitudinal observational cohort study.
Setting: This was a community-based study.
Patients: There were 616 patients (mean age 67.0 yr, 52.3% males, median diabetes duration 7.7 yr) assessed in 1998 and followed up to the end of June 2006.
Main Outcome Measures: Severe hypoglycemia defined as that requiring ambulance attendance, emergency department services, and/or hospitalization. Cox proportional hazards modeling was used to determine predictors of first episode, and Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regression models identified predictors of frequency.
Results: Fifty-two (8.4%) experienced 66 episodes during 3953 patient-years (incidence 1.7 per 100 patient-years). Those experiencing severe hypoglycemia had one to four episodes. Significant independent predictors of time to first episode were duration of insulin treatment, estimated glomerular filtration rate less than 60 ml/min per 1.73 m2, peripheral neuropathy, education beyond primary level, and past severe hypoglycemia. The zero-inflated negative binomial provided the best model of severe hypoglycemia frequency. Lower fasting serum glucose and higher glycosylated hemoglobin were significantly associated with frequency, whereas patients at minimal risk of repeated severe hypoglycemia were unlikely to use insulin or to have short-duration insulin treatment, to have renal impairment or peripheral neuropathy, or to be educated beyond primary level.
Conclusions: Duration of insulin treatment was confirmed as an independent risk factor for severe hypoglycemia. The novel association with educational attainment suggests knowledge-driven intensive glycemic self-management. The positive relationship between frequency and glycosylated hemoglobin may identify patients with unstable glycemic control.
Greater educational attainment and a higher HbA1c appear to be novel risk factors for severe hypoglycemia in community-based patients with type 2 diabetes.
In patients with ischemic stroke and a proximal cerebral arterial occlusion and salvageable tissue on imaging, alteplase followed by thrombectomy with a stent retriever was more effective than ...alteplase alone in improving reperfusion, neurologic recovery, and functional outcome.
The results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial,
1
which showed reduced disability among patients with ischemic stroke who were treated with endovascular thrombectomy in addition to standard care, represent an advance in stroke care. The MR CLEAN study followed several trials that had neutral findings with respect to the use of endovascular thrombectomy.
2
–
4
In the largest of these trials, the Interventional Management of Stroke 3 (IMS-3) study, investigators compared the administration of 0.9 mg of alteplase per kilogram of body weight to a bridging strategy of . . .
Summary Objective A neuropathic pain (NP) questionnaire may facilitate the identification of a neuropathic component to osteoarthritis (OA) pain. An existing questionnaire, the painDETECT, was ...modified for use in knee OA and administered to measure the prevalence and correlates of NP symptoms among adults with this condition. Method Sensibility of the modified painDETECT (mPD-Q) was assessed in 20 OA subjects followed by mail administration in an established knee OA cohort. NP symptoms were defined using a previously established, painDETECT cut-point. Correlates of NP symptoms, including OA severity (Western Ontario and McMaster Universities Osteoarthritis Index, Von Korff Chronic Pain Grade pain subscale score), psychological factors (Centre for Epidemiological Studies Depression Scale, Pain Catastrophizing Scale), and concomitant medical conditions, were evaluated using logistic regression. Construct validity of the mPD-Q was evaluated through co-administration with another NP questionnaire (S-LANSS). Results The mPD-Q had face and content validity. Of 259 eligible cohort members, 171 (66%) completed the questionnaire; 28% had NP symptoms on the mPD-Q (19% among those without neurological conditions). Independent correlates of NP symptoms were: pain intensity (adjusted odds ratio OR = 2.1 per 10 unit increase, P < 0.0001), the presence of referred back/hip pain (adjusted OR = 2.9, P = 0.024), number of painful joints (OR = 1.2, P = 0.20) and one or more self-reported neurological condition (OR = 3.0, P = 0.026). Conclusions Among older adults with chronic symptomatic knee OA, over one-quarter had NP symptoms localized to their knees using the mPD-Q. The mPD-Q may facilitate the identification of a neuropathic component to pain in adults with knee OA who may benefit from further evaluation and/or treatment for NP.
PDF
