Systematic review and meta-analysis of randomized controlled trials of psychological interventions to improve glycaemic control in children and adults with type 1 diabetes.

AIM: We conducted a systematic review aggregate and network meta-analysis of psychological interventions for people with type 1 diabetes to assess their effectiveness in improving glycaemic levels. METHODS: We searched the following databases from 1 January 2003 to 1 July 2018: MEDLINE, CINAHL, PsycINFO, Embase, Cochrane Controlled Trials, Web of Science, clinicaltrials.gov, Dissertation Abstract International. We included randomized controlled trials (RCT) of psychological interventions for children and adults with type 1 diabetes reported in any language. We extracted data on publications, participant characteristics at baseline, intervention and control group, and data for the primary outcome, change in glycaemic control [HbA1c (mmol/mol/%)]. Study authors were contacted for missing data. The review was registered with international prospective register of systematic reviews registration (PROSPERO) CRD42016033619. RESULTS: Twenty-four adult RCTs and 23 of children with type 1 diabetes were included in the systematic review. In aggregate meta-analysis there was no overall effect of psychological intervention compared with control on HbA1c [adults, nine RCTs, n = 1102, pooled mean difference -0.12, 95% confidence intervals (CI) -0.27 to 0.03, I2 = 29.0%, P = 0.19; children, 20 RCTs, n = 2567, -0.09, 95% CI -0.22 to 0.04, I2 =54.0% P=0.002]. Network meta-analysis suggested that probability and rank-ordering of effectiveness is highest for attention control groups (b = -0.47, 95% CI -0.80 to -0.12) followed by cognitive behavioural therapy (CBT) (-0.26, 95% CI -0.45 to -0.06) compared with usual care for adults. CONCLUSIONS: Overall psychological interventions for children and adults with type 1 diabetes do not improve glycaemic control. For adults, CBT-based interventions have the potential to be effective.

A pilot study of an integrated mental health, social and medical model for diabetes care in an inner-city setting: Three Dimensions for Diabetes (3DFD).

AIMS: We examined the effectiveness of a service innovation, Three Dimensions for Diabetes (3DFD), that consisted of a referral to an integrated mental health, social care and diabetes treatment model, compared with usual care in improving biomedical and health economic outcomes. METHODS: Using a non-randomized control design, the 3DFD model was offered in two inner-city boroughs in London, UK, where diabetes health professionals could refer adult residents with diabetes, suboptimal glycaemic control [HbA1c ≥ 75 mmol/mol (≥ 9.0%)] and mental health and/or social problems. In the usual care group, there was no referral pathway and anonymized data on individuals with HbA1c ≥ 75 mmol/mol (≥ 9.0%) were collected from primary care records. Change in HbA1c from baseline to 12 months was the primary outcome, and change in healthcare costs and biomedical variables were secondary outcomes. RESULTS: 3DFD participants had worse glycaemic control and higher healthcare costs than control participants at baseline. 3DFD participants had greater improvement in glycaemic control compared with control participants [-14 mmol/mol (-1.3%) vs. -6 mmol/mol (-0.6%) respectively, P < 0.001], adjusted for confounding. Total follow-up healthcare costs remained higher in the 3DFD group compared with the control group (mean difference £1715, 95% confidence intervals 591 to 2811), adjusted for confounding. The incremental cost-effectiveness ratio was £398 per mmol/mol unit decrease in HbA1c , indicating the 3DFD intervention was more effective and costed more than usual care. CONCLUSIONS: A biomedical, psychological and social criteria-based referral system for identifying and managing high-cost and high-risk individuals with poor glycaemic control can lead to improved health in all three dimensions.

Successful management of the first reported case in Austria of COVID-19 with ARDS.

We report the successful management of a patient with severe respiratory failure due to COVID-19 admitted to an intensive care unit complicated by secondary catheter-related infection of Candida glabrata. We are discussing some of the clinical challenges and the pitfalls in molecular diagnosis of SARS-CoV-2, including the fact that a positive PCR result may not always reflect infectiousness.

Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. We showed previously that 18 ADHD adolescents over 11 runs of 8.5 min of real-time functional magnetic resonance neurofeedback of the right inferior frontal cortex (rIFC) progressively increased activation in 2 regions of the rIFC which was associated with clinical symptom improvement. In this study, we used functional connectivity analyses to investigate whether fMRI-Neurofeedback of rIFC resulted in dynamic functional connectivity changes in underlying neural networks. Whole-brain seed-based functional connectivity analyses were conducted using the two clusters showing progressively increased activation in rIFC as seed regions to test for changes in functional connectivity before and after 11 fMRI-Neurofeedback runs. Furthermore, we tested whether the resulting functional connectivity changes were associated with clinical symptom improvements and whether they were specific to fMRI-Neurofeedback of rIFC when compared to a control group who had to self-regulate another region. rIFC showed increased positive functional connectivity after relative to before fMRI-Neurofeedback with dorsal caudate and anterior cingulate and increased negative functional connectivity with regions of the default mode network (DMN) such as posterior cingulate and precuneus. Furthermore, the functional connectivity changes were correlated with clinical improvements and the functional connectivity and correlation findings were specific to the rIFC-Neurofeedback group. The findings show for the first time that fMRI-Neurofeedback of a typically dysfunctional frontal region in ADHD adolescents leads to strengthening within fronto-cingulo-striatal networks and to weakening of functional connectivity with posterior DMN regions and that this may be underlying clinical improvement.

A qualitative study of the acceptability of cognitive bias modification for paranoia (CBM-pa) in patients with psychosis.

BACKGROUND: Cognitive Bias Modification (CBM) has been used successfully as a computer-based intervention in disorders such as anxiety. However, CBM to modify interpretations of ambiguous information relevant to paranoia has not yet been tested. We conducted a qualitative investigation of a novel intervention called CBM for paranoia (CBM-pa) to examine its acceptability in patients with psychosis. METHODS: Eight participants with psychosis who completed CBM-pa were identified by purposive sampling and invited for a semi-structured interview to explore the facilitators and barriers to participation, optimum form of delivery, perceived usefulness of CBM-pa and their opinions on applying CBM-pa as a computerised intervention. The interviews were transcribed and analysed using thematic analysis by researchers working in collaboration with service users. RESULTS: Themes emerged relating to participants' perception about delivery, engagement, programme understanding, factors influencing experience, perceived impact and application of CBM-pa. CBM-pa was regarded as easy, straightforward and enjoyable. It was well-accepted among those we interviewed, who understood the procedure as a psychological intervention. Patients reported that it increased their capacity for adopting alternative interpretations of emotionally ambiguous scenarios. Although participants all agreed on the test-like nature of the current CBM-pa format, they considered that taking part in sessions had improved their overall wellbeing. Most of them valued the computer-based interface of CBM-pa but favoured the idea of combining CBM-pa with some form of human interaction. CONCLUSIONS: CBM-pa is an acceptable intervention that was well-received by our sample of patients with paranoia. The current findings reflect positively on the acceptability and experience of CBM-pa in the target population. Patient opinion supports further development and testing of CBM-pa as a possible adjunct treatment for paranoia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 90749868 . Retrospectively registered on 12 May 2016.

Fact or fiction: reducing the proportion and impact of false positives.

False positive findings in science are inevitable, but are they particularly common in psychology and psychiatry? The evidence that we review suggests that while not restricted to our field, the problem is acute. We describe the concept of researcher 'degrees-of-freedom' to explain how many false-positive findings arise, and how the various strategies of registration, pre-specification, and reporting standards that are being adopted both reduce and make these visible. We review possible benefits and harms of proposed statistical solutions, from tougher requirements for significance, to Bayesian and machine learning approaches to analysis. Finally we consider the organisation and methods for replication and systematic review in psychology and psychiatry.

Effects of cognitive remediation on negative symptoms dimensions: exploring the role of working memory.

BACKGROUND: Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement. METHOD: Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests. RESULTS: Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = -0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation. CONCLUSIONS: The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors.

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors. METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Systematic review and meta-analysis of the efficacy of interventions for people with Type 1 diabetes mellitus and disordered eating.

AIM: To examine the types of interventions currently available for people with Type 1 diabetes mellitus and their effectiveness. BACKGROUND: The prevalence of disordered eating in people with Type 1 diabetes mellitus is twice that in their counterparts without diabetes, and is associated with worse biomedical outcomes and greater mortality. METHODS: Medline, Embase, PsycINFO, the Cochrane Library, PubMed and OpenGrey databases were searched up to August 2016 to identify studies on interventions in people with Type 1 diabetes-associated disordered eating. For the systematic review, intervention components were identified and their effectiveness was examined. For the meta-analysis, the pooled effect sizes of glycaemic control (HbA1c ) between pre- and post-treatment in treatment and comparison groups were calculated using a random effects model. RESULTS: Of 91 abstracts reviewed, six studies met the inclusion criteria, of which three had appropriate data for the meta-analysis (n = 118). The pooled effect size was -0.21 95% CI (-0.58 to 0.16; where negative values represent an improvement in HbA1c levels), indicating no statistically significant improvement in the treatment group compared with comparison group. Inpatient therapy appeared to be the most effective treatment, and this had multiple components including cognitive behavioural therapy, psychoeducation and family therapy. CONCLUSION: Limited or no improvement in glycaemic control and disordered eating symptoms was observed in people with Type 1 diabetes-associated disordered eating who were receiving currently available interventions. The present review suggests that developing an intensive intervention with a joint focus on both disordered eating and diabetes management is needed for this complex patient group.

Machine learning, statistical learning and the future of biological research in psychiatry.

Psychiatric research has entered the age of 'Big Data'. Datasets now routinely involve thousands of heterogeneous variables, including clinical, neuroimaging, genomic, proteomic, transcriptomic and other 'omic' measures. The analysis of these datasets is challenging, especially when the number of measurements exceeds the number of individuals, and may be further complicated by missing data for some subjects and variables that are highly correlated. Statistical learning-based models are a natural extension of classical statistical approaches but provide more effective methods to analyse very large datasets. In addition, the predictive capability of such models promises to be useful in developing decision support systems. That is, methods that can be introduced to clinical settings and guide, for example, diagnosis classification or personalized treatment. In this review, we aim to outline the potential benefits of statistical learning methods in clinical research. We first introduce the concept of Big Data in different environments. We then describe how modern statistical learning models can be used in practice on Big Datasets to extract relevant information. Finally, we discuss the strengths of using statistical learning in psychiatric studies, from both research and practical clinical points of view.

The set-shifting profiles of anorexia nervosa and autism spectrum disorder using the Wisconsin Card Sorting Test: a systematic review and meta-analysis.

Difficulties in set-shifting are commonly reported in both autism spectrum disorder (ASD) and anorexia nervosa (AN) populations. Despite this, it is not known whether this cognitive profile persists across different ages, or whether the profiles seen in ASD and AN are comparable. This systematic review and meta-analyses aimed to compare the set-shifting profiles, as measured by the Wisconsin Card Sorting Test (WCST) in adults and younger people with either ASD or AN, relative to healthy controls (HCs) and to statistically compare performance on the WCST between ASD and AN. In all, 24 studies on ASD and 22 studies on AN were identified. In ASD, there were significant differences between the clinical group and HCs, with the ASD group making significantly more perseverative errors, indicating greater difficulty in set-shifting [pooled effect size of d = 0.67, 95% confidence interval (CI) 0.53-0.81, p ⩽ 0.001]. This effect was consistent across the age span. For AN studies, there was a significant difference between adults with AN and HCs (d = 0.52, 95% CI 0.36-0.68, p ⩽ 0.001) but a non-significant effect in child studies (d = 0.25, 95% CI -0.05 to 0.55, z = 1.66, p = 0.096). Meta-regression indicated no effect of diagnosis (AN or ASD) on performance in adult studies but there was a non-significant trend (p = 0.053) towards children with ASD performing worse than children with AN. While difficulties with set-shifting appear to be stable in ASD, there may be differences between children and adults with AN, which warrant further investigation.

Antidepressant, antipsychotic and psychological interventions in subjects at high clinical risk for psychosis: OASIS 6-year naturalistic study.

BACKGROUND: Recent randomized controlled trials suggest some efficacy for focused interventions in subjects at high risk (HR) for psychosis. However, treating HR subjects within the real-world setting of prodromal services is hindered by several practical problems that can significantly make an impact on the effect of focused interventions. METHOD: All subjects referred to Outreach and Support in South London (OASIS) and diagnosed with a HR state in the period 2001-2012 were included (n = 258). Exposure to focused interventions was correlated with sociodemographic and clinical characteristics at baseline. Their association with longitudinal clinical and functional outcomes was addressed at follow-up. RESULTS: In a mean follow-up time of 6 years (s.d. = 2.5 years) a transition risk of 18% was observed. Of the sample, 33% were treated with cognitive behavioural therapy (CBT) only; 17% of subjects received antipsychotics (APs) in addition to CBT sessions. Another 17% of subjects were prescribed with antidepressants (ADs) in addition to CBT. Of the sample, 20% were exposed to a combination of interventions. Focused interventions had a significant relationship with transition to psychosis. The CBT + AD intervention was associated with a reduced risk of transition to psychosis, as compared with the CBT + AP intervention (hazards ratio = 0.129, 95% confidence interval 0.030-0.565, p = 0.007). CONCLUSIONS: There were differential associations with transition outcome for AD v. AP interventions in addition to CBT in HR subjects. These effects were not secondary to baseline differences in symptom severity.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT RCT study--Corrigendum.

The author regrets to announce that affiliation 8, in the above article (Gardner-Sood et al. 2015), contained an error in the author affiliation address and author surname, which were published in the approved article. The correct surname and affiliation address are given below. J. Eberhard, Clinical Psychiatric Research Center, Lund University, Skåne, Sweden

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT randomized controlled trial.

BACKGROUND: The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment. METHOD: Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18-65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria. RESULTS: High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS. CONCLUSIONS: In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.

Mechanisms of change underlying the efficacy of cognitive behaviour therapy for chronic fatigue syndrome in a specialist clinic: a mediation analysis.

BACKGROUND: Several randomized controlled trials (RCTs) have shown that cognitive behavioural psychotherapy (CBT) is an efficacious treatment for chronic fatigue syndrome (CFS). However, little is known about the mechanisms by which the treatment has its effect. The aim of this study was to investigate potential mechanisms of change underlying the efficacy of CBT for CFS. We applied path analysis and introduce novel model comparison approaches to assess a theoretical CBT model that suggests that fearful cognitions will mediate the relationship between avoidance behaviour and illness outcomes (fatigue and social adjustment). METHOD: Data from 389 patients with CFS who received CBT in a specialist service in the UK were collected at baseline, at discharge from treatment, and at 3-, 6- and 12-month follow-ups. Path analyses were used to assess possible mediating effects. Model selection using information criteria was used to compare support for competing mediational models. RESULTS: Path analyses were consistent with the hypothesized model in which fear avoidance beliefs at the 3-month follow-up partially mediate the relationship between avoidance behaviour at discharge and fatigue and social adjustment respectively at 6 months. CONCLUSIONS: The results strengthen the validity of a theoretical model of CBT by confirming the role of cognitive and behavioural factors in CFS.

The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D).

AIMS/HYPOTHESIS: This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi-ethnic cohort. METHODS: A population-based cross-sectional design was used. People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner-city boroughs of South London, serving a population in which 20% of residents are of black African or Caribbean ethnicity. Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records. Multiple logistic regression methods were used to report associations between ethnicity and diabetes-complication status. RESULTS: From 96 general practices, 1,506 patients were recruited. Their mean age was 55.6 (± 11.07) years, 55% were men, 60% were asymptomatic at diagnosis and 51%, 38% and 11% were of white, black and South Asian/other ethnicity, respectively. Compared with white participants, black and South Asian/other participants were: younger (mean age 58.9 [± 10.09], 52.4 [± 11.19] and 51.5 [± 10.42] years, respectively; p < 0.0001); less likely to have neuropathy (10.1%, 3.6% and 4.4%; p < 0.0001) or report coronary artery disease (12.7%, 4.8% and 7.3%; p < 0.0001). In logistic regression, compared with white participants, black participants had lower levels of macrovascular complications (OR 0.52, 95% CI 0.32, 0.84; p = 0.01). Male sex was independently associated with microvascular disease (OR 1.69, 95% CI 1.26, 2.28; p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of complications at time of diagnosis was lower than expected, especially in black and South Asian/other ethnic groups. However, in multi-ethnic inner-city populations, onset of type 2 diabetes occurred almost 10 years earlier in non-white populations than in white participants, predicating a prolonged morbidity.

Negative psychotic symptoms and impaired role functioning predict transition outcomes in the at-risk mental state: a latent class cluster analysis study.

BACKGROUND: Many research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the course and outcome based on individual symptoms scores. METHOD: Data from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes. RESULTS: LCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate-severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning. CONCLUSIONS: The different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms.

Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.

BACKGROUND: Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms. Method In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task. RESULTS: The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC. CONCLUSIONS: In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.

Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen.

Five-year follow-up of a cohort of people with their first diabetic foot ulcer: the persistent effect of depression on mortality.

AIMS/HYPOTHESIS: Depressive disorders are associated with mortality within 18 months of presentation of diabetic foot ulcers (DFU). The main aim of this study was to determine whether depressive disorder is still associated with increased mortality in people with their first foot ulcer at 5 years. METHODS: This is a 5-year follow-up of a cohort of 253 patients presenting with their first DFU. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) 2.1 was used to define those who met DSM-IV (Diagnostic and Statistical Manual 4th edition) criteria for depressive disorder. Cox regression analysis controlled for potential covariates: age, sex, marital status, socioeconomic status, smoking, mean HbA(1c), diabetes complications and ulcer severity. The main outcome was mortality at 5 years. RESULTS: The prevalence of DSM-IV depressive disorder at baseline was 32.2% (n = 82). There were 92 (36.4%) deaths over the 5 years of follow-up. In the Cox regression (n = 246), after adjusting for covariates, baseline DSM-IV depressive disorder was significantly associated with a twofold increased risk of mortality for any depressive episode (HR 2.09, 95% CI 1.34, 3.25), minor (HR 1.93, 95% CI 1.00, 3.74) or major depressive disorders (HR 2.18, 95% CI 1.31, 3.65), compared with patients who were not depressed. CONCLUSIONS/INTERPRETATION: Depression is associated with a persistent twofold increased risk of mortality in people with their first DFU at 5 years.