Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. METHODS: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. RESULTS: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. CONCLUSION: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

A report on the safety of acitretin use in patients with renal failure on haemodialysis.

Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end-stage renal disease (ESRD) on haemodialysis (HD). However, these patients often lack medication choices and in certain clinical scenarios the benefits of acitretin may outweigh the potential risks. We identified 24 patients with ESRD on HD undergoing acitretin treatment from the Duke and Vanderbilt University Medical Centers. While adverse effects were common, they were not a frequent cause of treatment discontinuation among patients. We also found no association between acitretin treatment and hospital admissions or mortality. Lastly, we found statistically significant increases in alkaline phosphatase (ALP; P = 0.03) and total bilirubin (P < 0.001) when patients were receiving acitretin and HD compared with baseline. However, there was no dose dependency or temporal association with acitretin or HD initiation. Based on these preliminary findings, we find that acitretin may safely be used in patients receiving HD, with close monitoring of ALP and bilirubin.

Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19.

OBJECTIVE AND DESIGN: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is the major symptom of the post-COVID syndrome (known colloquially as long-COVID). The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19. SUBJECTS AND METHODS: We analyzed pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19-positive and -negative participants were categorized based on SARS-CoV-2 antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale. RESULTS: COVID-19-positive participants exhibited mild disease. Chronic fatigue was a prevalent symptom among this population and significantly higher in positive vs. negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in positive and negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in negative, but not positive individuals. Raised BMI was associated with chronic fatigue in positive participants. CONCLUSIONS: Pre-existing increased IL-6 levels may contribute to chronic fatigue symptoms, but there was no increased risk in individuals with mild COVID-19 compared with uninfected individuals. Elevated BMI also increased the risk of chronic fatigue in mild COVID-19, consistent with previous reports.

Recent Advances in Melanoma Diagnosis and Prognosis Using Machine Learning Methods.

PURPOSE OF REVIEW: The purpose was to summarize the current role and state of artificial intelligence and machine learning in the diagnosis and management of melanoma. RECENT FINDINGS: Deep learning algorithms can identify melanoma from clinical, dermoscopic, and whole slide pathology images with increasing accuracy. Efforts to provide more granular annotation to datasets and to identify new predictors are ongoing. There have been many incremental advances in both melanoma diagnostics and prognostic tools using artificial intelligence and machine learning. Higher quality input data will further improve these models' capabilities.

Modic change is associated with increased BMI but not autoimmune diseases in TwinsUK.

PURPOSE: Low back pain (LBP) is one of the largest causes of morbidity worldwide. The aetiology of LBP is complex, and many factors contribute to the onset. Bone marrow lesions within the vertebra adjacent to an intervertebral degenerate disc named Modic change (MC) have been suggested as a diagnostic subgroup of LBP. Autoimmune response has been proposed to be one of the causes that promote the development of MC. The aim of the current investigation is to assess prevalence and severity of MC and LBP in participants with an autoimmune disease diagnosis in a well-documented cohort of adult twin volunteers. METHODS: Multivariate generalized mixed linear models (GLMM) were implemented in order to calculate the association between having an autoimmune disorder and MC prevalence, width and severe and disabling LBP. The model was corrected for family structure as well as for covariates such as age, BMI and smoking. RESULTS: No association was found between diagnosis of autoimmune disorder and MC. Interestingly, BMI was independently associated with MC width but not to MC prevalence. These results help to shed light on the relationship between MC and autoimmunity as well as the role of BMI in the development of the lesions. CONCLUSION: This study is the first to examine autoimmune disorders and MC prevalence in a large, population-based female cohort. The study was well powered to detect a small effect. No association was found between having a diagnosis of one or more autoimmune conditions and MC prevalence, width or LBP.

Are current machine learning applications comparable to radiologist classification of degenerate and herniated discs and Modic change? A systematic review and meta-analysis.

INTRODUCTION: Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists. METHODS: A PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed. RESULTS: 1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets. DISCUSSION: This review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.

Piloting CanCope: An internet-delivered transdiagnostic intervention to improve mental health in cancer survivors.

OBJECTIVE: CanCope is an internet-delivered, cognitive-behavioural intervention adapted from the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders to improve emotion regulation and support the mental health of cancer survivors. Four separate pilot studies evaluated each of CanCope's modules for (1) feasibility and participant satisfaction, and changes in (2) module-specific outcomes, and (3) global measures of emotion dysregulation and anxiety and depressive symptoms, from pre-to-post module delivery. METHODS: Eligible cancer survivors self-selected into one two-week online module designed to improve a specific aspect of emotion regulation ([1] understanding emotions, [2] mindfulness of emotions, [3] cognitive reappraisals, [4] challenging emotion-driven behaviours). RESULTS: Across modules, post-intervention surveys were completed by 17-19 participants, (58.1%-90.5% completion rate for participants who received the intervention). Each module was feasible and participants reported high satisfaction. Moderate-to-large pre-to-post effect sizes in mean differences were observed in module-specific target outcomes (p's < 0.05). Emotion dysregulation significantly decreased across modules 1 to 3 (p's < 0.05) with a non-significant decrease for module 4 (p = 0.13). Anxiety symptoms significantly decreased across all modules (p's < 0.05). Depressive symptoms significantly decreased across modules 1 and 3 (p's < 0.05), with non-significant decreases across modules 2 (p = 0.08) and 4 (p = 0.06). CONCLUSIONS: Each CanCope module demonstrated promise in targeting emotion regulation skills and supporting the mental health of cancer survivors. Randomised controlled trials are required to test the efficacy of CanCope as an intervention in its entirety.

Evidence for infection in intervertebral disc degeneration: a systematic review.

PURPOSE: Back pain is a major problem worldwide and is linked to intervertebral disc degeneration and Modic change. Several studies report growth of bacteria following extraction of degenerate discs at spine surgery. A pathophysiological role for infection in back pain has been proposed. METHOD: We conducted a PRISMA systematic review. MEDLINE, PubMed, Scopus and Web of Science were searched with the terms Modic change, intervertebral dis*, bacteria, microb*, and infect*. Date limits of 2001-2021 were set. Human studies investigating the role of bacteria in disc degeneration or Modic change in vertebrae were included. RESULTS: Thirty-six articles from 34 research investigations relating to bacteria in human degenerate discs were found. Cutibacterium acnes was identified in pathological disc material. A 'candidate bacterium' approach has been repeatedly adopted which may have biased results to find species a priori, with disc microbial evidence heavily weighted to find C. acnes. CONCLUSION: Evidence to date implicates C. acnes identified through culture, microscopy and sequencing, with some suggestion of diverse bacterial colonisation in the disc. This review found studies which used culture methods and conventional PCR for bacterial detection. Further agnostic investigation using newer methods should be undertaken.

Power and sample size for multistate model analysis of longitudinal discrete outcomes in disease prevention trials.

For clinical trials where participants pass through a number of discrete health states resulting in longitudinal measures over time, there are several potential primary estimands for the treatment effect. Incidence or time to a particular health state are commonly used outcomes but the choice of health state may not be obvious and these estimands do not make full use of the longitudinal assessments. Multistate models have been developed for some diseases and conditions with the purpose of understanding their natural history and have been used for secondary analysis to understand mechanisms of action of treatments. There is little published on the use of multistate models as the primary analysis method and potential implications on design features, such as assessment schedules. We illustrate methods via analysis of data from a motivating example; a Phase III clinical trial of pressure ulcer prevention strategies. We clarify some of the possible estimands that might be considered and we show, via a simulation study, that under some circumstances the sample size could be reduced by half using a multistate model based analysis, without adversely affecting the power of the trial.

Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial.

BACKGROUND: Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7-12 nmol/l). METHODS AND FINDINGS: This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25-50 years with morning total serum testosterone 7-12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25-37 years, 57.4% 38-50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (-0.9 kg, 95% CI -1.6 to -0.3, p = 0.0073), decreased whole-body fat mass (-1.8 kg, 95% CI -2.9 to -0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9-2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. CONCLUSIONS: In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. TRIAL REGISTRATION: ISRCTN: 70274195, EudraCT: 2011-000677-31.

Comparison of generic and disease-specific measures in their ability to detect differences in pressure ulcer clinical groups.

Patient-reported outcomes can be included as end points in pressure ulcer (PU) intervention trials to provide information to inform decision-making and improve the lives of patients. However, the challenge for researchers and clinicians is identifying and choosing an appropriate instrument for each particular application that suits their research questions and clinical context. To provide researchers and clinicians with the information needed to inform choice of patient-reported outcome measures, we compared a generic and disease-specific measures' ability to discriminate between clinical groups known to differ, and determined their responsiveness to change. We performed analyses on a subset of patients recruited to the PRESSURE 2 trial that completed the pressure ulcer quality of life instrument-prevention version (PU-QOL-P) and Short Form 12 Questionnaire (SF12) measures at baseline and 30-day posttreatment. Known-group validity and responsiveness-to-change analyses were conducted. The analysis sample consisted of 617 patients that completed both measures at baseline. Known-group validity revealed that some PU-QOL-P symptoms and function scales differentiated between people with category 2 PUs and those without PUs. A less meaningful pattern of results was observed for the SF12 scales, suggesting that the PU-QOL-P is more sensitive to differences between PU and non-PU populations. Responsiveness analysis revealed that the PU-QOL-P was more responsive in detecting disease severity than the SF12. The PU-QOL-P provides a standardized method for assessing PU-specific symptoms and functioning outcomes and is suitable for quantifying the benefits of PU interventions from the patient's perspective. Generic measures are useful for group comparisons of global quality of life domains. Choice of measure for each particular application should be determined by the purpose of the measurement and the information required.

Depression and poor outcome after an acute coronary event: Clarification of risk periods and mechanisms.

OBJECTIVE: Lifetime depression and depression around the time of an acute coronary syndrome event have been associated with poor cardiac outcomes. Our study sought to examine the persistence of this association, especially given modern cardiac medicine's successes. METHODS: For 332 patients admitted for an acute coronary syndrome, a baseline interview assessed major depression status, and psychological measures were administered. At 1 and 12 months post-acute coronary syndrome event, telephone interviews collected rates of hospital readmission and/or death and major depression status, while biomarker information was examined using medical records. RESULTS: The 12-month mortality rate was 2.3% and cardiac readmission rate 21.0%. Depression subsequent to an acute coronary syndrome event resulted in a threefold and 2.5-fold increase in 1-month and 12-month odds of cardiac readmission or death, respectively. No relationship with past depressive episodes was found. Poor sleep was associated with higher trait anxiety and neuroticism scores and with more severe depression. CONCLUSION: Lifetime depression may increase the risk of depression around the time of an acute coronary syndrome but not influence cardiac outcomes. We suggest that poor sleep quality may be causal or indicate high anxiety/neuroticism, which increases risk to depression and contributes to poor cardiac outcomes rather than depression being the primary causal factor.

A patient-reported pressure ulcer health-related quality of life instrument for use in prevention trials (PU-QOL-P): psychometric evaluation.

INTRODUCTION: Pressure ulcer-specific patient-reported outcome (PRO) instruments should be used to inform patient care and provide a strong evidence base for interventions aimed at preventing pressure ulcers. The aim was to carry out a comprehensive evaluation of the psychometric properties of a PRO instrument designed to assess symptoms and functional outcomes in patients at high-risk of developing pressure ulcers, the PU-QOL-P instrument. METHODS: We modified the original PU-QOL instrument to be suitable for patients at high risk of pressure ulcer development based on feedback from patients, specialist nurses and PRO methodologists. The modified PU-QOL-P instrument was administered to a sub-set of patients participating in the PRESSURE 2 trial. Patients completed PU-QOL-P and SF12 instruments at baseline, weeks 1 and 3, and 30 days post-treatment. We undertook psychometric evaluation of the modified PU-QOL-P to test scale targeting, scaling assumptions, reliability, validity and responsiveness. RESULTS: The analysis sample consisted of 617 patients that completed both instruments at baseline. We found that the PU-QOL-P instrument, consisting of nine PU-specific outcomes: three symptom and six function scales, meets established criteria for reliability, construct validity, and responsiveness. Internal consistency reliability was high with all scale Cronbach alpha > 0.795 (range 0.795-0.970). The factor analysis mostly supported the six-function scale structure. Scaling assumptions were satisfied; all item-total correlations above 0.30. Convergent validity was confirmed by significant correlations between hypothesized scales as expected. PU-QOL-P scales were responsive to change: mean scale scores from baseline to 30 days post-treatment were statistically significant for all scales apart the daily activities scale (effect sizes ranged from moderate to high). As expected, worse symptoms and functioning was observed in patients who had a category 1 or 2 PU compared to patients who did not have a PU. CONCLUSIONS: The PU-QOL-P provides a standardised method for assessing pressure ulcer-specific symptoms and functional outcomes for quantifying the benefits of associated interventions from the patient's perspective. It can be used in research with adults at risk of pressure ulcer development in all UK healthcare settings.

Clinical evaluation of a new pressure ulcer risk assessment instrument, the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T).

AIM: To test the psychometric properties and clinical usability of a new Pressure Ulcer Risk Assessment Instrument including inter-rater and test-retest reliability, convergent validity and data completeness. BACKGROUND: Methodological and practical limitations associated with traditional Pressure Ulcer Risk Assessment Instruments, prompted a programme to work to develop a new instrument, as part of the National Institute for Health Research funded, Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056). DESIGN: Observational field test. METHOD: For this clinical evaluation 230 patients were purposefully sampled across four broad levels of pressure ulcer risk with representation from four secondary care and four community NHS Trusts in England. Blinded and simultaneous paired (ward/community nurse and expert nurse) PURPOSE-T assessments were undertaken. Follow-up retest was undertaken by the expert nurse. Field notes of PURPOSE-T use were collected. Data were collected October 2012-January 2013. RESULTS: The clinical evaluation demonstrated "very good" (kappa) inter-rater and test-retest agreement for PURPOSE-T assessment decision overall. The percentage agreement for "problem/no problem" was over 75% for the main risk factors. Convergent validity demonstrated moderate to high associations with other measures of similar constructs. CONCLUSION: The PURPOSE-T evaluation facilitated the initial validation and clinical usability of the instrument and demonstrated that PURPOSE-T is suitable of use in clinical practice. Further study is needed to evaluate the impact of using the instrument on care processes and outcomes.

Suprasensory phenomena in those with a bipolar disorder.

OBJECTIVES: To increase awareness of the sensory changes experienced during hypo/manic and depressive states by those with a bipolar disorder and determine if the prevalence of such features is similar across differing bipolar sub-types. METHODS: We interviewed 66 patients who acknowledged sensory changes during hypo/manic states. They were allocated to bipolar I, bipolar II and soft bipolar diagnostic categories and the prevalence of 10 differing sensory changes was quantified during hypo/manic and depressive phases. RESULTS: Bipolar I patients were just as likely, if not more likely, to report suprasensory changes which typically involved enhancement of senses during hypo/manic phases and muting or blunting during depressive phases. The high prevalence of changes in intuition, empathy, appreciation of danger and predictive capacities suggests that these are more part of the intrinsic bipolar mood domain states and not necessarily suprasensory, while changes in primary senses of smell, taste, vision, touch and hearing appear to more commonly define the suprasensory domain. CONCLUSIONS: It is important for clinicians and patients with a bipolar disorder to be aware of non-psychotic, suprasensory phenomena. Identification of such features may aid diagnosis and also explain the recognised increased creativity in those with a bipolar condition.

Pressure ulcer and wounds reporting in NHS hospitals in England part 2: Survey of monitoring systems.

This is the second of a two related papers describing work undertaken to compare and contrast Pressure Ulcer (PU) monitoring systems across NHS in-patient facilities in England. The work comprised 1) a PU/Wound Audit (PUWA) and 2) a survey of PU monitoring systems. This second paper focusses on the survey which explores differences in the implementation of PU adverse event monitoring systems in 24 NHS hospital Trusts in England. The survey questionnaire comprised 41 items incorporating single and multiple response options and free-text items and was completed by the PUWA Trust lead in liaison with key people in the organisation. All 24 (100%) Trusts returned the questionnaire, with high levels of data completeness (99.1%). The questionnaire results showed variation between Trusts in relation to the recording of PUs and their reporting as part of NHS prevalence and incident monitoring systems and to Trust boards and healthcare commissioners including the inclusion (or not) of device ulcers, unstageable ulcers, Deep Tissue Injury, combined PUs/Incontinence Associated Dermatitis, category ≥ 1 ulcers or category ≥ 2 ulcers, inherited ulcers, acquired ulcers, avoidable and unavoidable ulcers and the definition of Present On Admission. These fundamental differences in reporting preclude Trust to Trust comparisons of PU prevalence and incident reporting and monitoring systems due to variation in local application and data collection methods. The results of this work and the PUWA led to the development of recommendations for PU monitoring practice, many of which are internationally relevant.

Pressure ulcer and wounds reporting in NHS hospitals in England part 1: Audit of monitoring systems.

Internationally, health-care systems have attempted to assess the scale of and demonstrate improvement in patient harms. Pressure ulcer (PU) monitoring systems have been introduced across NHS in-patient facilities in England, including the Safety Thermometer (STh) (prevalence), Incident Reporting Systems (IRS) and the Strategic Executive Information System (STEIS) for serious incidents. This is the first of two related papers considering PU monitoring systems across NHS in-patient facilities in England and focusses on a Wound Audit (PUWA) to assess the accuracy of these systems. Part 2 of this work and recommendations are reported pp *-*. The PUWA was undertaken in line with 'gold-standard' PU prevalence methods in a stratified random sample of NHS Trusts; 24/34 (72.7%) invited NHS Trusts participated, from which 121 randomly selected wards and 2239 patients agreed to participate. PREVALENCE OF EXISTING PUS: The PUWA identified 160 (7.1%) patients with an existing PU, compared to 105 (4.7%) on STh. STh had a weighted sensitivity of 48.2% (95%CI 35.4%-56.7%) and weighted specificity of 99.0% (95%CI 98.99%-99.01%). EXISTING/HEALED PUS: The PUWA identified 189 (8.4%) patients with an existing/healed PU compared to 135 (6.0%) on IRS. IRS had an unweighted sensitivity of 53.4% (95%CI 46.3%-60.4%) and unweighted specificity of 98.3% (95%CI 97.7%-98.8%). 83 patients had one or more potentially serious PU on PUWA and 8 (9.6%) of these patients were reported on STEIS. The results identified high levels of under-reporting for all systems and highlighted data capture challenges, including the use of clinical staff to inform national monitoring systems and the completeness of clinical records for PUs.

Acute coronary syndrome-associated depression: the salience of a sickness response analogy?

Depression emerging in conjunction with acute coronary syndrome (ACS) is thought to constitute a distinct high-risk phenotype with inflammatory determinants. This review critically examines the notion put forward in the literature that ACS-associated depression constitutes a meaningful subtype that is qualitatively different from depressive syndromes observed in psychiatric patients; and evaluates the salience of an analogy to the acute sickness response to infection or injury as an explanatory model. Specific features differentiating ACS-associated depression from other phenotypes are discussed, including differences in depression symptom profiles, timing of the depressive episode in relation to ACS, severity of the cardiac event, and associated immune activation. While an acute sickness response analogy offers a plausible conceptual framework, concrete evidence is lacking for inflammatory activity as the triggering mechanism. It is likely that ACS-associated depression encompasses several causative scenarios.

Characterising acute coronary syndrome-associated depression: Let the data speak.

Depression in the context of acute coronary syndrome (ACS) is understood to confer increased morbidity and mortality risk. The pathophysiological mechanisms underlying this association remain poorly understood, although several candidates including inflammation, cardiac autonomic dysregulation, and behavioural factors are viewed as of key importance. No single bio-behavioural explanatory model of ACS-associated depression has emerged, likely due the substantial heterogeneity across both conditions. We studied 344 patients with ACS; 45 fulfilled diagnostic (DSM-IV) criteria for a major depressive episode occurring within 1-month of ACS, and 13 had ongoing major depression that pre-dated ACS and continued through to 1 month post-ACS. We employed two statistical methods (multinomial logistic regression; and latent class analysis) and a range of immunological, autonomic and nutritional markers in an attempt to characterise a biological basis for ACS-associated depression. Regression modelling failed to accurately predict categorical group membership of ACS-associated depression. An alternative data-driven approach produced a three-class solution, with the derived classes differing on measure of C-reactive protein, vitamin D, omega-6:omega-3 ratio, heart rate variability, and age (all p⩽0.004). The majority of participants with ACS-associated and ongoing depression were members of the class characterised by the greatest biological disturbance. Patients with depression differed from those without depression on a range of psychological trait and state variables; additionally reporting poorer sleep quality, higher levels of social isolation, and functional impairment, but had similar biological profiles. Patients with ongoing depression generally had higher scores on these psychological/behavioural measures. Our novel analytic approach identified a combination of biomarkers suggestive of a role for immune, autonomic, and nutritional pathways in the manifestation of depression during ACS, in the context of additional psychosocial and behavioural vulnerabilities. Further studies are required to confirm the causal role of these factors in perpetuating depression and increasing risk of poor-health outcomes.

The validity of a food frequency questionnaire as a measure of PUFA status in pregnancy.

BACKGROUND: Nutritional studies have found conflicting evidence regarding the ability of Food Frequency Questionnaires (FFQs) to demonstrate convergent validity with tissue content of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). We therefore sought to assess the convergent validity of a FFQ strategy when compared with a blood biomarker of PUFA levels in a sample of pregnant women. METHOD: A previously validated PUFA FFQ was completed by 895 pregnant women and compared to erythrocyte membrane of six PUFA variables. RESULTS: Four of the six correlations were found to be formally significant, however two of these demonstrated minimal associational strength. Moderate-high correlations between the FFQ-derived PUFA intake estimates and blood biomarker PUFA levels were shown only for eicosapentaenoic acid (EPA; 0.55) and docosahexaenoic acid (DHA; 0.61). CONCLUSIONS: Overall, the correlations were lower than those found in general population studies. Findings suggest biological estimates, such as blood samples, may be most appropriate to measure PUFA levels above indirect strategies such as an FFQ in this population. The results, if an indirect strategy is unavoidable, indicate specific PUFAs where an FFQ strategy may be most informative.