Longitudinal invariance of the Patient Health Questionnaire-9 among patients receiving pharmacotherapy for major depressive disorder: A secondary analysis of clinical trial data.

Comparing self-reported symptom scores across time requires longitudinal measurement invariance (LMI), a psychometric property that means the measure is functioning identically across all time points. Despite its prominence as a measure of depression symptom severity in both research and health care, LMI has yet to be firmly established for the Patient Health Questionnaire-9 depression module (PHQ-9), particularly over the course of antidepressant pharmacotherapy. Accordingly, the objective of this study was to assess for LMI of the PHQ-9 during pharmacotherapy for major depressive disorder. This was a secondary analysis of data collected during a randomized controlled trial. A total of 1,944 veterans began antidepressant monotherapy and completed the PHQ-9 six times over 24 weeks of treatment. LMI was assessed using a series of four confirmatory factor analysis models that included all six time points, with estimated parameters increasingly constrained across models to test for different aspects of invariance. Root-mean-square error of approximation of the chi-square difference test values below 0.06 indicated the presence of LMI. Exploratory LMI analyses were also performed for separate sex, age, and race subgroups. Root-mean-square error of approximation of the chi-square difference test showed minimal change in model fits during invariance testing (≤ 0.06 for all steps), supporting full LMI for the PHQ-9. LMI was also supported for all tested veteran subgroups. As such, PHQ-9 sum scores can be compared across extended pharmacotherapy treatment durations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

Sustainability benefits of transitioning from current diets to plant-based alternatives or whole-food diets in Sweden.

Plant-based alternatives (PBAs) are increasingly becoming part of diets. Here, we investigate the environmental, nutritional, and economic implications of replacing animal-source foods (ASFs) with PBAs or whole foods (WFs) in the Swedish diet. Utilising two functional units (mass and energy), we model vegan, vegetarian, and flexitarian scenarios, each based on PBAs or WFs. Our results demonstrate that PBA-rich diets substantially reduce greenhouse gas emissions (30-52%), land use (20-45%), and freshwater use (14-27%), with the vegan diet showing the highest reduction potential. We observe comparable environmental benefits when ASFs are replaced with WFs, underscoring the need to reduce ASF consumption. PBA scenarios meet most Nordic Nutrition Recommendations, except for vitamin B12, vitamin D and selenium, while enhancing iron, magnesium, folate, and fibre supply and decreasing saturated fat. Daily food expenditure slightly increases in the PBA scenarios (3-5%) and decreases in the WF scenarios (4-17%), with PBA diets being 10-20% more expensive than WF diets. Here we show, that replacing ASFs with PBAs can reduce the environmental impact of current Swedish diets while meeting most nutritional recommendations, but slightly increases food expenditure. We recommend prioritising ASF reduction and diversifying WFs and healthier PBAs to accommodate diverse consumer preferences during dietary transitions.

Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

OBJECTIVES: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). METHODS: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. RESULTS: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. CONCLUSIONS: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Effectiveness of lifestyle interventions for improving the physical health of children and adolescents taking antipsychotic medications: protocol for a systematic review and meta-analysis.

INTRODUCTION: Children and adolescents are increasingly prescribed antipsychotic medications off-label in the treatment of behavioural disorders. While antipsychotic medications are effective in managing behavioural issues, they carry a significant risk of adverse events that compromise ongoing physical health. Of particular concern is the negative impact antipsychotic medications have on cardiometabolic health. Interventions that aim to modify lifestyle habits have the potential to alleviate the adverse effects of antipsychotic medication by enhancing weight management, increasing physical activity, promoting better nutritional practices, improving dietary habits and promoting healthier sleep patterns and sleep hygiene. However, a comprehensive review has not been performed to ascertain the effectiveness of lifestyle interventions for children and adolescents who are at increased risk of antipsychotic-induced compromises to their physical health. METHODS AND ANALYSIS: This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases will be searched without any year constraints to identify randomised controlled trials that are published in the English language and report a lifestyle intervention compared with usual care with any physical health outcome measure. Trial registers and results repositories will be scoured to identify additional studies. Two reviewers will independently conduct screening, data extraction and quality assessment and compare the results. Quantitative data will be synthesised, where appropriate, through a random-effects meta-analysis model. Otherwise, data will be reported in a qualitative (narrative) synthesis. Heterogeneity will be quantified using the I2 statistic. The Cochrane Risk of Bias 2 tool will be used for risk of bias assessment. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to evaluate the cumulative body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required. The publication plan will target high-impact, peer-reviewed journals that fall under the scope of Psychiatry and Mental Health. PROSPERO REGISTRATION NUMBER: CRD42022380277.

Predicting 'Brainage' in late childhood to adolescence (6-17yrs) using structural MRI, morphometric similarity, and machine learning.

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy children to predict an individual's age from structural MRI. This data-driven, predicted 'Brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this Brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel Brainage approaches using morphometric similarity against more typical, single feature (i.e., cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a Brainage framework, morphometric similarity does not provide more accurate predictions of age. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy participants in this way.

Neurodevelopment of babies born to mothers with epilepsy: A prospective observational cohort study.

OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up. METHODS: Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition). RESULTS: There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval [CI] = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low. SIGNIFICANCE: These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.

Reframing the local-global food systems debate through a resilience lens.

Despite the growing knowledge that food system solutions should account for interactions and drivers across scales, broader societal debate on how to solve food system challenges is often focused on two dichotomous perspectives and associated solutions: either more localized food systems or greater global coordination of food systems. The debate has found problematic expressions in contemporary challenges, prompting us to revisit the role that resilience thinking can play when faced with complex crises that increase uncertainty. Here we identify four 'aching points' facing food systems that are central points of tension in the local-global debate. We apply the seven principles of resilience to these aching points to reframe the solution space to one that embeds resilience into food systems' management and governance at all scales, supporting transformative change towards sustainable food systems.

Predicting 'Brainage' in the Developmental Period using Structural MRI, Morphometric Similarity, and Machine Learning.

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy-children to predict an individual's age from structural MRI. This data-driven, 'brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel brain-age approaches using morphometric similarity against more typical, single feature (i.e. cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a brain-age framework, morphometric similarity does not explain more variance than individual structural features. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy individuals.

The development of the gut microbiome and temperament during infancy and early childhood: A systematic review.

Temperament in early childhood is a good predictor of later personality, behavior, and risk of psychopathology. Variation in temperament can be explained by environmental and biological factors. One biological mechanism of interest is the gut microbiome (GM), which has been associated with mental and physical health. This review synthesized existing literature evaluating the relationship between GM composition and diversity, and temperament in early life. Web of Science, PsycInfo, PubMed, and Scopus were searched, and data were extracted according to PRISMA guidelines. In total, 1562 studies were identified, of which six remained following application of exclusion/inclusion criteria. The findings suggest that there is an association between higher alpha diversity and temperament: greater Surgency/Extraversion and High-Intensity Pleasure in males, and lower Effortful Control in females. Unique community structures (beta diversity) were found for Surgency/Extraversion in males and Fear in females. An emerging pattern of positive temperament traits being associated with GM communities biased toward short-chain fatty acid production from a metabolism based on dietary fiber and complex carbohydrates was observed and is worthy of further investigation. To gain deeper understanding of the relationship, future research should investigate further the functional aspects of the microbiome and the influence of diet.

Anatomic and Reverse Stemless Shoulder Arthroplasty: Functional and Radiological Evaluation.

Background: Stemless shoulder arthroplasty was developed to restore the glenohumeral centre of rotation without violation of the humeral shaft. It allows the preservation of humeral bone stock. Complications related to stem malalignment and periprosthetic fractures can be avoided. Patient and methods: This is a prospective observational study that reports outcomes of 46 patients who received stemless shoulder arthroplasty "Comprehensive Nano implant ®." The series includes Group (A): 30 anatomic and one hemiarthroplasty. Group (B): 15 reverse stemless replacement. Functional outcomes were assessed by visual analog score (VAS), satisfaction, range motion, Constant score, and American Shoulder and Elbow Score (ASES). Results: The mean follow-up was 40.4 ± 12 months (range, 24 months to 60 months). Group (A): VAS and satisfaction improved by 5.3 and 67.5 points respectively. Constant score significantly improved from 28.5 ± 14.5 to 62.5 ± 23 P = <0.001. The radiological assessment showed the mean centre of rotation (COR) deviation was 2.8 ± 1.9 mm. 27% of patients have COR discrepancy of more than 4 mm. In Group (B), patients reported a significant improvement in VAS, Satisfaction, and ASES P = 0.002, 0.002, and 0.003, respectively.Complications include shoulder pain with progressive loss of movements, aseptic loosening early subscapularis rupture, glenohumeral dislocations, and humeral component migration. Conclusion: Anatomic Stemless total shoulder arthroplasty offers acceptable results and improvement of overall functional outcomes.

Cartilage debris and osteoarthritis risk factors influence gene expression in the synovium in end stage osteoarthritis.

BACKGROUND: Gene expression in healthy synovium remains poorly characterised. Thus, synovial functional activity changes associated with osteoarthritis (OA) are difficult to define. This study sought to identify differentially expressed genes (DEG) of end-stage OA and assess the influence of OA risk factors on these DEG. METHODS: Anonymised patient clinical data and x-ray images were analysed. Osteoarthritic and non-osteoarthritic patients with soft tissue or traumatic knee injuries were matched for body mass index (BMI) and sex. Tissue samples were partitioned for immunocytochemistry (IHC) and microarray analysis. Multiple bioinformatics applications were utilised to determine changes in functional and canonical pathway activation. RESULTS: Age, disease-modifying injections and hypertension were confounding factors between patient groups. Inflammation was present in all tissues. Cartilage debris and inflammatory aggregates were noted in many osteoarthritic patient tissues. IHC and expression analyses revealed upregulation of synoviolin 1 (SYVN1) in osteoarthritic synovium. Significant differential expression was noted in 2084 genes. Osteoarthritic synovium displayed a significant upregulation of 95% of DEG coding for proteins, relative to non-osteoarthritic synovium tissues. Unfolded protein response (UPR)-related genes were upregulated in osteoarthritic synovium; gene expression of molecules within many canonical pathways including protein ubiquitination and UPR pathways was modified by BMI and sex. CONCLUSIONS: The synovium of all three pathologies exhibited elements of an inflammatory response. Cartilage debris, age, BMI and sex influence DEG of osteoarthritic synovium. UPR pathway is the top deregulated canonical pathway identified in osteoarthritic synovium regardless of BMI and sex, while typical OA-associated inflammatory and matrix gene responses were minimal.

Patient-specific Instrumentation Versus Standard Surgical Instruments in Primary Reverse Total Shoulder Arthroplasty: A Retrospective Comparative Clinical Study.

Aims: Patient-specific instrumentation (PSI) in primary shoulder arthroplasty has been studied; results supported the positive impact of the PSI on the glenoid positioning. Nevertheless, no clinical outcomes have been reported. We compare the clinical outcomes of primary reverse total shoulder arthroplasty using PSI versus the standard methods. Methods: Fifty-three patients with full records and a minimum of 24-months follow-up were reviewed, 35 patients received primary standard RSTA, and 18 patients received primary PSI RSTA. All patients were operated on in a single center. The median follow-up was 46 months (53 months in the standard group vs 39 months in the PSI group). Results: There was an overall significant post-operative improvement in the whole cohort (P< 0.05). The standard group had more deformed glenoids (B2, B3, C&D) and significantly low preoperative constant score and forward flexion (P=0.02 & 0.034). Compared to the PSI group (all were A1, A2, B1 &one type D), there were no statistically significant differences in any clinical outcome postoperatively. PSI neither prolonged the waiting time to surgery (P=0.693) nor the intraoperative time (P=0.962). Radiologically, PSI secured a higher percentage of optimum baseplate position and screw anchorage; however, no statistical correlation was found. Conclusion: In this series, both groups achieved comparable good outcomes. PSI did not achieve significantly better clinical outcomes than Standard after primary RSTA. Yet comparison has some limitations. PSI did not negatively impact the waiting time or the surgical time.

Frailty Is Associated With Cognitive Decline Independent of Cerebral Small Vessel Disease and Brain Atrophy.

BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time ß -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.

Histopathological dataset and demographic details of synovial tissues from patients with end-stage osteoarthritis, soft tissue and traumatic injuries of the knee.

Degradation of articular cartilage is the defining feature of end-stage osteoarthritis (OA) with osteophytes, subchondral sclerosis, malalignment and joint space narrowing being additional indicators of advanced disease. Obesity, older age and female gender are OA risk factors. Differing degrees of synovitis are observed in OA, soft tissue and traumatic injuries of the knee. The synovium is also subject to systemic, enhanced lipids and inflammatory mediators characteristic of obesity. Synovial cellular composition changes specific to OA and associated with its handling of cartilage debris are unclear. Triangulation of data from three knee pathologies was used to highlight findings pertaining to OA compared to non-OA. OA patient data was compared to non-OA from knee ligament and tibial frature patients at surgery. Knee pathology, gender and BMI informed patient identification. Once consented, patient inclusion and characterisation utilised data from clinical assessments, blood tests, function scores, and radiological imaging, scores and intraoperative assessment. Intra-operative synovial tissues from the same site and processed identically underpins in-depth analyses and comparisons of histopathological images from these different knee pathologies. This supports the identification of distinct changes in the cellular composition of the knee synovium characteristic of OA. This data underpins a better understanding of OA pathogenesis and disease progression vital for the design of targeted therapeutics. The tissue and cell data include detailed results from the semi-quantitative synovitis score established by Krenn and observational data for morphological features such as cartilage debris inclusion, inflammatory cells aggregate and infiltration. This histopathological data is presented in the context of detailed clinical and functional information. This data and the holistic study design can be used as a foundation for the multifactorial collection and analysis of clinical data from OA patients, OA severity measures, tissue immuno-histology and synovial inflammation analysis to underpin the details and comparisons needed in further studies into OA and its treatment globally.

Mucins Inhibit Coronavirus Infection in a Glycan-Dependent Manner.

Mucins are a diverse and heterogeneous family of glycoproteins that comprise the bulk of mucus and the epithelial glycocalyx. Mucins are intimately involved in viral transmission. Mucin and virus laden particles can be expelled from the mouth and nose to later infect others. Viruses must also penetrate the mucus layer before cell entry and replication. The role of mucins and their molecular structure have not been well-characterized in coronavirus transmission studies. Laboratory studies predicting high rates of fomite transmission have not translated to real-world infections, and mucins may be one culprit. Here, we probed both surface and direct contact transmission scenarios for their dependence on mucins and their structure. We utilized disease-causing, bovine-derived, human coronavirus OC43. We found that bovine mucins could inhibit the infection of live cells in a concentration- and glycan-dependent manner. The effects were observed in both mock fomite and direct contact transmission experiments and were not dependent upon surface material or time-on-surface. However, the effects were abrogated by removal of the glycans or in a cross-species infection scenario where bovine mucin could not inhibit the infection of a murine coronavirus. Together, our data indicate that the mucin molecular structure plays a complex and important role in host defense.

Open sternoclavicular osteophyte debridement in the surgical management of sternoclavicular osteoarthritis: clinical outcome of a new procedure.

Introduction: Symptomatic sternoclavicular osteoarthritis is uncommon but remains the most frequent non-traumatic condition affecting the sternoclavicular joint and tends to have a predilection for middle-aged women. It responds well to conservative management. Surgery is indicated when conservative management fails. We present the clinical outcome of open symptomatic sternoclavicular osteophyte debridement, a new operation for treating recalcitrant symptomatic sternoclavicular osteoarthritis. Methods: Five patients (five symptomatic sternoclavicular joints) with symptomatic sternoclavicular osteoarthritis underwent open sternoclavicular debridement following failure of conservative treatment. There were three females and two males. Mean age was 46.6 years (range 37.17-66). Four cases were primary osteoarthritis and one case was secondary to trauma. They were reviewed at mean follow-up at 35.4 months with minimum follow-up of 29 months. Assessment included Quick Disabilities of Arm Shoulder and Hand (DASH) and subjective patient satisfaction score. Results: There was no post-operative complication. Mean Quick DASH score 10.9 (range 0-29.5) at mean 35.4-month follow-up (range 29-43 months). Three patients reported excellent and two reported good outcome as per subjective satisfaction score. Conclusions: Open sternoclavicular debridement has proved to be a simple, safe and highly effective new surgical treatment for patients with symptomatic sternoclavicular osteoarthritis unresponsive to non-operative management.

Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients.

BACKGROUND: Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed. OBJECTIVES: We aimed to examine the relationship between vitamin D status and mortality from COVID-19. METHODS: In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression. RESULTS: There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality. CONCLUSIONS: Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).

Medication Optimization Using Pharmacogenomic Testing in a Complex Mental Health Population Prescribed Psychiatric Polypharmacy.

The use of polypharmacy has become significantly more common over the past two decades, increasing the risk of drug-drug interactions and adverse drug reactions. Pharmacogenomic (PGx) assays have the purported benefit of being able to predict an individual's response to a specific medication based on genetic markers, which may facilitate the development of optimized medication regimens for patients prescribed polypharmacy. This 12-week pilot study examined the impact of the PGx results on the clinical management of Veterans who were prescribed psychiatric polypharmacy. Psychiatric medication providers were given access to the PGx assay results, including notification of drug-drug-gene interactions computed from an algorithm decision tool, to assist with medication management decisions. Veteran outpatients (N = 53) prescribed polypharmacy (mean = 13.15 medications) were enrolled into the study. In 92.4% of cases, providers changed medications at baseline, with 83% of providers indicating that they changed their original medication plan based on the PGx results. Clinical improvement over the 12-week treatment phase was seen in depression (F(1.63, 45) = 5.45, P = .01, η2  = .11) and mental health quality of life (F(2.00, 45) = 4.16, P < .05, η2  = .16). Adverse drug effects were unchanged or improved over time. Rates of polypharmacy remained unchanged. The results suggest that medication changes based on the PGx assay may be beneficial in a complex patient population prescribed polypharmacy.