Detecting Depression in Patients with Coronary Heart Disease: a Diagnostic Evaluation of the PHQ-9 and HADS-D in Primary Care,Findings From the UPBEAT-UK Study

Objective

People with coronary heart disease (CHD) are at heightened risk of depression, and this co-occurrence of conditions is associated with poorer outcomes including raised mortality. This study compares the diagnostic accuracy of two depression case finding instruments in CHD patients relative to a diagnostic standard, the revised Clinical Interview Schedule (CIS-R).

Methods

The Patient Health Questionnaire (PHQ-9), the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the CIS-R depression module were administered to 803 patients identified from the CHD registers of GP practices in Greater London.

Results

Of 730 recruited patients without previously identified depression, 32 (4.4%) met ICD-10 depressive episode criteria according to the CIS-R. For the PHQ-9 and HADS-D lower cut-points than those routinely recommended were associated with improved case identifying properties. The PHQ-9 appeared the superior instrument using a cut-point of ≥8 (sensitivity=94%; specificity=84%). Using categorical scoring the PHQ-9 was 59% sensitive and 95% specific. For the HADS-D using cut-point ≥5, sensitivity was 81% and specificity was 77%.Areas under the curves (AUC) (standard error) were 0.95 (0.01) and 0.88 (0.02) for the PHQ-9 and HADS-D, and 0.91 (0.02) for PHQ-9 using the categorical algorithm. Statistically significant differences between AUCs of the PHQ-9 and the HADS-D favoured the former. Severity ratings compared across measures indicated inconsistency between recommended bandings: the PHQ-9 categorised a larger proportion of participants with mild and moderate depression.

Conclusion

This is the first large-scale investigation of the accuracy of these commonly used measures within a primary care CHD population. Our results suggest that although both scales have acceptable abilities and can be used as case identification instruments for depression in patients with CHD, the PHQ-9 appeared diagnostically superior. Importantly, optimal cut-off points for depression identification in this population appear to differ from standard values, and severity ratings differ between these measures.     

First Evidence of Sternal Wound Biofilm following Cardiac Surgery

Management of deep sternal wound infection (SWI), a serious complication after cardiac surgery with high morbidity and mortality incidence, requires invasive procedures such as, debridement with primary closure or myocutaneous flap reconstruction along with use of broad spectrum antibiotics. The purpose of this clinical series is to investigate the presence of biofilm in patients with deep SWI. A biofilm is a complex microbial community in which bacteria attach to a biological or non-biological surface and are embedded in a self-produced extracellular polymeric substance. Biofilm related infections represent a major clinical challenge due to their resistance to both host immune defenses and standard antimicrobial therapies. Candidates for this clinical series were patients scheduled for a debridement procedure of an infected sternal wound after a cardiac surgery. Six patients with SWI were recruited in the study. All cases had marked dehiscence of all layers of the wound down to the sternum with no signs of healing after receiving broad spectrum antibiotics post-surgery. After consenting patients, tissue and/or extracted stainless steel wires were collected during the debridement procedure. Debrided tissues examined by Gram stain showed large aggregations of Gram positive cocci. Immuno-fluorescent staining of the debrided tissues using a specific antibody against staphylococci demonstrated the presence of thick clumps of staphylococci colonizing the wound bed. Evaluation of tissue samples with scanning electron microscope (SEM) imaging showed three-dimensional aggregates of these cocci attached to the wound surface. More interestingly, SEM imaging of the extracted wires showed attachment of cocci aggregations to the wire metal surface. These observations along with the clinical presentation of the patients provide the first evidence that supports the presence of biofilm in such cases. Clinical introduction of the biofilm infection concept in deep SWI may advance the current management strategies from standard antimicrobial therapy to anti-biofilm strategy.     

Culture, characterization and differentiation of cells from buffalo (Bubalus bubalis) amnion

Stem cells present an important tool in livestock assisted reproduction and veterinary therapeutic field such as tissue engineering. We report for the first time isolation of pluripotent stem cell-like cells expressing pluripotency markers (alkaline phospahatase, OCT-4, NANOG and SOX-2) from the amnion of water buffalo (Bubalus bubalis). The cells showed no apparent abnormalities in their chromosomal profiles before and after cryopreservation. The cytochemical staining revealed that pluripotent cells were capable of undergoing directed differentiation in vitro into osteocytes. It could be inferred that amnion-derived pluripotent stem cell-like cells can be isolated, cultured for many passages and differentiated into mesoderm lineage, and may be an alternative source to mesenchymal stem cells. These cells can have applications in assisted reproduction, developmental biological and regenerative medicine.     

Triazolo and imidazo dihydropyrazolopyrimidine potassium channel antagonists

Previously disclosed C6 amido and benzimidazole dihydropyrazolopyrimidines were potent and selective blockers of I_Kur current. Syntheses and SAR for C6 triazolo and imidazo dihydropyrazolopyrimidines series are described. Trifluoromethylcyclohexyl N(1) triazole, compound 51, was identified as a potent and selective K_v1.5 inhibitor with an acceptable PK and liability profile.     

If at first you don't succeed… Studies of ontogeny shed light on the cognitive demands of habitual tool use

Many species use tools, but the mechanisms underpinning the behaviour differ between species and even among individuals within species, depending on the variants performed. When considering tool use ‘as adaptation’, an important first step is to understand the contribution made by fixed phenotypes as compared to flexible mechanisms, for instance learning. Social learning of tool use is sometimes inferred based on variation between populations of the same species but this approach is questionable. Specifically, alternative explanations cannot be ruled out because population differences are also driven by genetic and/or environmental factors. To better understand the mechanisms underlying routine but non-universal (i.e. habitual) tool use, we suggest focusing on the ontogeny of tool use and individual variation within populations. For example, if tool-using competence emerges late during ontogeny and improves with practice or varies with exposure to social cues, then a role for learning can be inferred. Experimental studies help identify the cognitive and developmental mechanisms used when tools are used to solve problems. The mechanisms underlying the route to tool-use acquisition have important consequences for our understanding of the accumulation in technological skill complexity over the life course of an individual, across generations and over evolutionary time.     

Variation in the sexual behaviour of Achnanthes longipes (Bacillariophyta). III. Progeny of crosses between monoecious and unisexual clones

The allogamous raphid diatom Achnanthes longipes C. A. Agardh possesses a complex breeding system involving interactions between three types of clone: monoecious, unisexual and bisexual. Previous studies showed that these three types can be crossed with each other, with a tendency for sexual characteristics to be inherited: inbred monoecious lineages gave rise to monoecious or, very rarely, to bisexual clones, while inbred unisexual lineages yielded unisexual and bisexual clones. The current paper reports on the progeny of crosses between monoecious and unisexual clones and their inbred offspring. All three types of clone appeared in the F₁ and F₂, although unisexual clones of opposite sex to the parental clone were not found. Inbreeding depression was observed and also a tendency for ‘normal’ auxosporulation (producing two auxospores per pair of gametangia) to be replaced by ‘reduced’ or ‘intermediate’ auxosporulation (producing one auxospore per pair). In addition, patterns of incompatibility were observed that were not seen during earlier studies of clones isolated directly from nature. These included the inability of some F₁ clones to mate with each other, in spite of compatibility with all other clones examined (unisexual, bisexual and monoecious).     

Breeding season length predicts duet coordination and consistency in Neotropical wrens (Troglodytidae)

Many animals produce coordinated signals, but few are more striking than the elaborate male–female vocal duets produced by some tropical songbirds. Yet, little is known about the factors driving the extreme levels of vocal coordination between mated pairs in these taxa. We examined evolutionary patterns of duet coordination and their potential evolutionary drivers in Neotropical wrens (Troglodytidae), a songbird family well known for highly coordinated duets. Across 23 wren species, we show that the degree of coordination and precision with which pairs combine their songs into duets varies by species. This includes some species that alternate their song phrases with exceptional coordination to produce rapidly alternating duets that are highly consistent across renditions. These highly coordinated, consistent duets evolved independently in multiple wren species. Duet coordination and consistency are greatest in species with especially long breeding seasons, but neither duet coordination nor consistency are correlated with clutch size, conspecific abundance or vegetation density. These results suggest that tightly coordinated duets play an important role in mediating breeding behaviour, possibly by signalling commitment or coalition of the pair to mates and other conspecifics.     

Murine guanylate cyclase C regulates colonic injury and inflammation

Guanylate cyclase C (GUCY2C or GC-C) and its ligands, guanylin (GUCA2A or Gn) and uroguanylin (GUCA2B or Ugn), are expressed in intestinal epithelial cells and regulate ion secretion, intestinal barrier function, and epithelial monolayer homeostasis via cGMP-dependent signaling pathways. The aim of this study was to determine whether GC-C and its ligands direct the course of intestinal inflammation. In this article, we show that dextran sodium sulfate (DSS)-induced clinical disease and histological damage to the colonic mucosa were significantly less severe in GC-C(-/-) mice and moderately reduced in Gn(-/-) animals. Relative to wild-type controls, GC-C(-/-) and Gn(-/-) mice had reduced apoptosis and increased proliferation of intestinal epithelial cells during DSS colitis. Basal and DSS-induced production of resistin-like molecule β (RELMβ) was substantially diminished in GC-C(-/-) mice. RELMβ is thought to stimulate cytokine production in macrophages in this disease model and, consistent with this, TNF-α and IFN-γ production was minimal in GC-C(-/-) animals. RELMβ and cytokine levels were similar to wild-type in Gn(-/-) mice, however. Colonic instillation of recombinant RELMβ by enema into GC-C(-/-) mice restores sensitivity to DSS-mediated mucosal injury. These findings demonstrate a novel role for GC-C signaling in facilitating mucosal wounding and inflammation, and further suggest that this may be mediated, in part, through control of RELMβ production.     

Modelling the epidemiology of hepatitis B in New Zealand

Hepatitis B is a vaccine preventable disease caused by the hepatitis B virus (HBV) that can induce potentially fatal liver damage. It has the second highest mortality rate of all vaccine preventable diseases in New Zealand. Vaccination against HBV was introduced in New Zealand in 1988, and the country is now categorised with overall low endemicity but with areas of both high and medium endemic levels. We present an SECIR compartmental mathematical model, with the population divided into age classes, for the transmission of HBV using local data on incidence of infection and vaccination coverage. We estimate the basic reproduction number, R₀, to be 1.53, and show that the vaccination campaign has substantially reduced this below one. However, a large number of carriers remain in the population acting as a source of infection.