Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

Health impacts of poor water quality on an endangered shorebird breeding programme in Aotearoa New Zealand.

CASE HISTORY: Two clusters of mortality among endangered tuturuatu/tchuriwat'/shore plover (Thinornis novaeseelandiae) have occurred at captive breeding facilities around New Zealand in recent years. In the first, four chicks died at Pukaha National Wildlife Centre (Mount Bruce, NZ) in February 2016, and in the second five adult birds at the Cape Sanctuary (Cape Kidnappers, NZ) died in 2022. CLINICAL FINDINGS: In 2016, four chicks were noted to become weak, have increased vocalisations and closed eyes prior to death. The remaining chicks were treated for 5 days with amoxycillin/clavulanate orally twice daily. Water containers and brooders were cleaned and disinfected with chlorhexidine. No further mortality was seen.In the 2022 cluster, three adult breeding birds died acutely and five others showed inappetence, weight loss and diarrhoea approximately 10 days after heavy rains flooded the local river. The five birds were treated with amoxycillin/clavulanate orally twice daily and oral fluids for 5 days. Two birds died and three survived. No breeding occurred in the aviaries in the following season. PATHOLOGICAL FINDINGS: In 2016, the chicks showed pulmonary changes ranging from congestion and oedema to heterophilic inflammation consistent with septicaemia.In 2022, the adult birds showed proliferation of bacteria in the distal small intestine associated with mucosal ulceration and heterophilic infiltration. Acid-fast staining of the caecal contents in one bird showed organisms consistent with Cryptosporidium spp. LABORATORY FINDINGS: Aerobic bacterial cultures of the lung and liver of two affected chicks carried out in 2016 showed heavy growth of Plesiomonas shigelloides. The same organism was cultured from water trays and holding tanks containing water boatmen (Sigara arguta) on which the chicks were fed.In 2022, cultures from the livers of three dead birds each showed a mixed bacterial growth with differing dominant organisms (Aeromonas sobria, Hafnia alvei, Citrobacter freundii and an Enterococcus sp.). PCR and sequencing confirmed Cryptosporidium parvum in the caecum of one bird. Fresh faeces from 24 breeding birds from the captive breeding facilities were negative by PCR for Cryptosporidium spp.The captive breeding facilities obtain water for the aviaries and aquatic invertebrates to feed to the chicks from local freshwater sources. Water quality testing at the Cape Sanctuary revealed concentrations of faecal indicator bacteria in excess of safe drinking water guidelines, with peaks following heavy rainfall. CLINICAL RELEVANCE: Fluctuations in water quality associated with mammalian faecal bacteria can adversely affect bird health and impact on captive rearing of endangered wildlife.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.

Vitamin D and lactoferrin attenuate stress-induced colitis in Wistar rats via enhancing AMPK expression with inhibiting mTOR-STAT3 signaling and modulating autophagy.

Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap-restraint stress (WRS) on rat behavior, on adenosine monophosphate-activated protein kinase-mammalian/mechanistic target of rapamycin-signal transducer and activator of transcription 3 (AMPK-mTOR-STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared. Twenty-four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS-exposed and treated with vitamin D3 (500 IU/kg/day), and Group IV: WRS-exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin-10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR-STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress-induced colitis treatment than vitamin D3.

A comparative study of acetyl-l-carnitine and caloric restriction impact on hippocampal autophagy, apoptosis, neurogenesis, and astroglial function in AlCl3-induced Alzheimer's in rats.

Alzheimer's disease (AD) is a worldwide chronic progressive neurodegenerative disease. We aimed to investigate and compare the neuroprotective impact of acetyl-l-carnitine and caloric restriction (CR) on AlCl3-induced AD to explore the pathogenesis and therapeutic strategies of AD. Sixty-seven adult male Wistar rats were allocated into Control, AlCl3, AlCl3-acetyl-l-carnitine, and AlCl3-CR groups. Each of AlCl3 and acetyl-l-carnitine were given by gavage in a daily dose of 100 mg/kg and CR was conducted by giving 70% of the daily average caloric intake of the control group. Rats were subjected to behavioral assessment using open field test, Y maze, novel object recognition test and passive avoidance test, biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate-activated protein kinase, Beclin-1, Bcl-2-associated X protein, and B cell lymphoma 2 (Bcl2) as well as hippocampal Ki-67 and glial fibrillary acidic protein immunohistochemistry. AlCl3-induced cognitive and behavioral deficits coincident with impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Acetyl-l-carnitine and CR partially protect against AlCl3-induced behavioral, cognitive, biochemical, and histological changes, with more ameliorative effect of acetyl-l-carnitine on hippocampal apoptotic markers, and more obvious behavioral and histological improvement with CR.

A retrospective study of native wild birds and reptiles admitted to three New Zealand wildlife hospitals due to predation by cats.

AIMS: To investigate the types of wildlife affected and outcomes of hospitalisation for native wild birds and reptiles admitted to three wildlife hospitals in New Zealand following predation by cats. METHODS: We reviewed hospital records of three wildlife hospitals (Wildbase Hospital (WBH) in Palmerston North; The Wildlife Hospital - Dunedin (DWH); and The Nest Te Kohanga (TNTK) in Wellington) for cases of native species with a submission history or diagnosis of predation by cats over the period 2006-2022. Frequency analysis and cross-tabulation of the data were carried out using the factors wildlife hospital, animal order, species, and case outcome. RESULTS: Native wildlife (n = 639) presented following predation by cats to the three wildlife hospitals comprised 598 (93.6%) birds from 31 species and 41 (6.4%) reptiles from eight species. The mortality rate of these patients combined was 61.8% (395/639), with the other 38.2% (244/639) being released from hospital to rehabilitation facilities, released to the wild, or, for a small number, put into permanent captive placements. The most common species of birds admitted due to predation by cats were tui (Prosthemadera novaeseelandiae; n = 173), silvereyes (Zosterops lateralis; n = 142), sacred kingfishers (Todiramphus sanctus; n = 100) and kereru (Hemiphaga novaeseelandiae; n = 70). There was an overall trend to increasing numbers of wildlife admitted for predation by cats over the period of this review, but the different operating periods of the three hospitals should be considered. Each of the three hospitals saw a different mix of species, with Wellington's TNTK seeing the widest diversity of species affected. CONCLUSIONS: Predation by cats was a common cause of native birds and reptiles being admitted to all three wildlife hospitals and a diversity of urban and rural wildlife were affected. CLINICAL RELEVANCE: Predation by cats causes significant mortality in wildlife patients admitted to wildlife hospitals despite best current treatment. Cat management strategies in Aotearoa New Zealand should consider the welfare and health of wildlife.

Morphological characterisation of a novel Eimeria sp. parasite in South Island takahe (Porphyrio hochstetteri).

AIMS: A novel Eimeria sp. is described from the endangered South Island takahe (Porphyrio hochstetteri). METHODS: Faeces were collected from South Island takahe in managed populations across two geographic locations within New Zealand, linked by extensive bird translocation. Faecal flotations were performed and oocysts collected were sporulated in sterile water at 25°C for 5 days. Morphometric measurements including length:width (L:W) ratios of oocysts and sporocysts were made of 65 oocysts using light microscopy under oil immersion. A retrospective histological review of archived post-mortem material from takahe was performed. RESULTS: Oocysts were ovoid (mean L:W 1.2 (SD 0.1)) with mean dimensions of 18.0 (SD 0.8) × 15.2 (SD 0.7) µm, and walls 0.9 (SD 0.1) µm thick at the equator. A micropyle was absent and the oocyst residuum was present as a granular spherical mass. Four sporocysts were present and were elongate ovoid in shape (mean L:W ratio 1.5), with mean dimensions of 9.7 (SD 1.1) × 6.3 (SD 0.7) µm and each containing two sporozoites with anterior and posterior refractile bodies. This morphological description is distinct from other Eimeria spp. described in hosts of the family Rallidae. The retrospective review of tissue was hindered by the poor quality of the preserved gut tissue, but coccidial organisms were able to be identified in the caudal ileum and caecum of a single bird. CONCLUSIONS: A novel Eimeria sp. was identified in the faeces of takahe. We propose this species be named Eimeria takahe. CLINICAL RELEVANCE: Conservation of the endangered South Island takahe is reliant on human management of populations under varying degrees of captive management. An understanding of diseases affecting this host, including parasites and their identification as unique to the takahe or introduced from interactions with other hosts, is essential to the maintenance of overall bird health and informs management decisions in this recovery programme.Abbreviations: L:W: Length:width.

Matrix adhesion and remodeling diversifies modes of cancer invasion across spatial scales.

The metastasis of malignant epithelial tumors begins with the egress of transformed cells from the confines of their basement membrane (BM) to their surrounding collagen-rich stroma. Invasion can be morphologically diverse: when breast cancer cells are separately cultured within BM-like matrix, collagen I (Coll I), or a combination of both, they exhibit collective-, dispersed mesenchymal-, and a mixed collective-dispersed (multimodal)- invasion, respectively. In this paper, we asked how distinct these invasive modes are with respect to the cellular and microenvironmental cues that drive them. A rigorous computational exploration of invasion was performed within an experimentally motivated Cellular Potts-based modeling environment. The model comprised of adhesive interactions between cancer cells, BM- and Coll I-like extracellular matrix (ECM), and reaction-diffusion-based remodeling of ECM. The model outputs were parameters cognate to dispersed- and collective- invasion. A clustering analysis of the output distribution curated through a careful examination of subsumed phenotypes suggested at least four distinct invasive states: dispersed, papillary-collective, bulk-collective, and multimodal, in addition to an indolent/non-invasive state. Mapping input values to specific output clusters suggested that each of these invasive states are specified by distinct input signatures of proliferation, adhesion and ECM remodeling. In addition, specific input perturbations allowed transitions between the clusters and revealed the variation in the robustness between the invasive states. Our systems-level approach proffers quantitative insights into how the diversity in ECM microenvironments may steer invasion into diverse phenotypic modes during early dissemination of breast cancer and contributes to tumor heterogeneity.

Feed Restriction Modulates Growth, Gut Morphology and Gene Expression in Zebrafish.

A reduction in daily caloric or nutrient intake has been observed to promote health benefits in mammals and other vertebrates. Feed Restriction (FR), whereby the overall food intake of the organism is reduced, has been explored as a method to improve metabolic and immune health, as well as to optimize productivity in farming. However, less is known regarding the molecular and physiological consequences of FR. Using the model organism, Danio rerio, we investigated the impact of a short-term (month-long) FR on growth, gut morphology and gene expression. Our data suggest that FR has minimal effects on the average growth rates, but it may affect weight and size heterogeneity in a sex-dependent manner. In the gut, we observed a significant reduction in gut circumference and generally lower mucosal heights, whereas other parameters remained unchanged. Gene Ontology (GO), EuKaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified numerous metabolic, reproductive, and immune response pathways that were affected by FR. These results broaden our understanding of FR and contribute towards growing knowledge of its effects on vertebrate health.

Surgical repair of a meningoencephalocoele in a kakapo (Strigops habroptilus).

CASE HISTORY: A kakapo (Strigops habroptilus) chick hatched on an off-shore island of New Zealand with a small white mass protruding through the cranial skin of the head. The chick's growth followed a normal pattern for kakapo but at 3 weeks of age the cranium mass was non-reducible and fixed in place and the chick was removed from the island for diagnostic imaging and hand-rearing. CLINICAL FINDINGS AND TREATMENT: A computed tomography (CT) examination revealed a full-thickness circular defect in the central cranium with suspected herniation of brain and dura. Surgery was performed at 37 days of age, and the herniated dura was dissected from the open fontanelle. Attempts to reduce the herniated tissue were unsuccessful, so the herniated dura and cortex were clamped and resected. The dura was closed and the periosteum of the skull was scarified and monofilament polypropylene mesh was secured tautly over the fontanelle. The mesh graft was infused with autologous bone marrow harvested from the ulna in an attempt to stimulate osteogenesis in the mesh repair. The skin flap was then closed. Post-operative recovery and healing were without complication. A CT examination 4 weeks after surgery showed no recurrence of the hernia, and a composite of mesh and scar over the open fontanelle which had reduced in diameter. The chick was released back onto an off-shore island with a radio transmitter and it continues to be monitored regularly. PATHOLOGICAL FINDINGS: The tissue resected at surgery consisted of a cylindrical core of cerebral parenchyma overlain by a mildly hyperplastic epidermis, and large amounts of oedematous fibrovascular tissue arising from the leptomeninges. DIAGNOSIS: Rostral parietal meningoencephalocoele. CLINICAL RELEVANCE: This is the first report of successful surgical resolution of a meningoencephalocoele in any bird. Techniques from human neurosurgery were adapted for the unique anatomical features of the avian skull. The risks of the procedure included increased intra-cranial pressure resulting in anaesthetic complications or death, cerebrospinal fluid leakage, meningitis or recurrence of the meningoencephalocoele. In the longer term, there was a risk of developmental deficits in cognition or behaviour. None of these complications eventuated in the short to medium term, probably due to the small size of the meningoencephalocoele.

Changes in quality of life in relation to disease activity in systemic lupus erythematosus: post-hoc analysis of the BLISS-52 Trial.

OBJECTIVES: To quantify changes in generic patient-reported outcomes against clinically meaningful, disease activity measures in systemic lupus erythematosus (SLE). METHODS: Using BLISS-52 trial data (867 SLE patients), we estimated the mean difference in change of patient-reported outcome scores (Medical Outcomes Study SF-36 and FACIT-fatigue) in relation to disease activity (SELENA-SLEDAI, SELENA-SLEDAI flare index, SLE responder index and British Isles Lupus Assessment Group (BILAG)), considering all study visits by the mean of multivariate mixed models. Predefined disease activity criteria were used to define for improvement and worsening. RESULTS: Mean changes in physical component summary/mental component summary and FACIT-fatigue in response to changes in SELENA-SLEDAI and SELENA-SLEDAI flare index were significantly lower than 2.5. New SELENA-SLEDAI flare index flare led to a significant change in all patient-reported outcome scores, except role emotional. Mean improvement in patient-reported outcomes with achievement of SLE responder index ranged between +6.2 (physical function) and +11.3 (bodily pain) for SF-36 domains, + 3.4 and +3.3 for mental component summary and physical component summary, and was +4.2 for FACIT-fatigue. When considering disease activity changes by organ system, changes in BILAG (constitutional) was independently associated with significant changes in FACIT-fatigue and all SF-36 domains (except physical function), changes in BILAG (musculoskeletal and hematological) were independently associated with significant changes in patient-reported outcome scores, except for role emotional (musculoskeletal) and general health/mental health (hematological). Mean changes in every SF-36 domain varied (and was >5) with SLE responder index attainment. CONCLUSIONS: Knowledge of changes in patient-reported outcomes, against clinically meaningful changes in SLE disease activity measures, is crucial for designing of clinical trials, interpretation of results and shared decision-making for patient care.

Hindi LupusPRO: cross cultural validation of disease specific patient reported outcome measure of lupus.

BACKGROUND: LupusPRO is a SLE specific patient reported outcomes measure developed and validated in the USA. This study aimed to validate the Hindi version of LupusPRO in systemic lupus erythematosus (SLE) patients in India. METHODS: Disease activity and damage were assessed using SELENA-SLEDAI and SLICC/ACR damage Index respectively. Demographic and clinical features were recorded. The Hindi Version of LupusPRO and 36-Item Short Form Health Survey (SF-36) were administered for assessment of quality of life. Depression, anxiety and fatigue were assessed using Patient Health Questionnaire 9 (PHQ9), Generalized Anxiety Disorder 7 (GAD7) and Fatigue Severity Scale (FSS) respectively. Internal consistency reliability, test-retest reliability, convergent and discriminant validity (against corresponding domains of the SF-36, fatigue, depression and anxiety), criterion validity (against disease activity and damage) and known group validity were tested. RESULTS: A total of 144 (140 females) patients with SLE with a mean age of 32.48 ± 7.26 years participated in the study. The median (interquartile range) SELENA SLEDAI was 2 (5.5). The internal consistency reliability of the LupusPRO domains was >0.7 for most domains (except for lupus symptoms, lupus medication, procreation and social support).We noted good convergent validity of LupusPRO domains with corresponding domains of SF-36, pain vitality with fatigue (FSS) and emotional health domain with depression (PHQ9) and anxiety (GAD7). Criterion validity of lupus symptoms with disease activity was observed. Known group validity of the LupusPRO domains with patient reported health status was observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The Hindi LupusPRO has fair psychometric properties among Indian patients with SLE.

Fatigue in systemic lupus: the role of disease activity and its correlates.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a variety of negative health outcomes resulting from inflammation in various organ systems. Although treatment continues to advance, fatigue remains one of the most salient, poorly understood and addressed patient complaints. Understanding the mechanisms of fatigue can help guide the development of interventions to improve health outcomes. The aim of this research was to evaluate the contribution of six variables (disease activity, insomnia, depression, stress, pain and physical health) to fatigue in SLE without concomitant fibromyalgia (FM). METHODS: A total of 116 ethnically diverse, primarily female participants (91%) with SLE, receiving care at university medical centers, completed assessments of disease activity and quality of life outcomes (FACIT-FT, Insomnia Severity Index, Perceived Stress Scale (PSS-4), Pain Inventory, Depression-PHQ-9, and LupusPRO-physical function). All patients met the American College of Rheumatology classification criteria for SLE and did not have a known diagnosis of FM. Multivariate linear and stepwise regression analyses were conducted with fatigue (FACIT-FT) as the dependent variable, and the above six variables as independent variables. RESULTS: Mean (SD) age was 39.80 (13.87) years; 50% were African American, 21% Caucasian, 13% Hispanic, 9% Asian and 8% other. Mean (SD) FACIT-FT was 20.09 (12.76). Collectively, these six variables explained 57% of the variance in fatigue. In the multivariate model, depression, stress and pain were significantly and independently associated with fatigue, but not disease activity, sleep or physical health. Stress had the largest effect on fatigue (ß 0.77, 95% CI 0.17-1.38, p = 0.01), followed by depression (ß 0.66, 95% CI 0.21-1.10, p = 0.005). On stepwise regression analysis, only stress, depression and pain were retained in the model, and collectively explained 56% of the variance in fatigue. All three remained independent correlates of fatigue, with the largest contribution being stress (ß 0.84, 95% CI 0.27-1.42, p = 0.005), followed by depression (ß 0.79, 95% CI 0.44-1.14, p < 0.001) with fatigue. CONCLUSION: Stress, depression and pain are the largest independent contributors to fatigue among patients with SLE, without concurrent FM. Disease activity, sleep and physical health were not associated with fatigue. The evaluation of stress, depression and pain needs to be incorporated during assessments and clinical trials of individuals with SLE, especially within fatigue. This stress-depression-fatigue model requires further validation in longitudinal studies and clinical trials. Significance and innovation: • Disease activity, sleep, pain, stress, depression, and physical health have been reported individually to be associated with fatigue in lupus. This analysis evaluated the role of each and all of these six variables collectively in fatigue among patients with SLE without a known diagnosis of FM. • Disease activity, sleep and physical health were not significantly related to fatigue, but depression, stress and pain were. • The results emphasize the need to evaluate and treat fatigue in individuals with SLE utilizing a biopsychosocial approach, particularly in the realm of clinical trials. Behavioral medicine interventions are shown to be most effective for the treatment of depression, stress and pain.

Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding.

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics.

Correction: Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding.

[This corrects the article DOI: 10.1371/journal.pgen.1005954.].

Psychometric properties of MDHAQ/RAPID3 in patients with systemic lupus erythematosus.

BACKGROUND: The Multidimensional Health Assessment Questionnaire (MDHAQ) is a patient-reported outcome (PRO) tool that includes the Routine Assessment of Patient Index Data 3 (RAPID3), an index that can be calculated at the point of care. The objective of this study was to perform psychometric analyses of MDHAQ/RAPID3 to study its measurement properties in systemic lupus erythematosus (SLE). METHODS: The MDHAQ was completed by 161 SLE patients in routine care, along with LupusPRO (a disease-specific PRO). The SLE disease-specific activity index (SELENA-SLEDAI) and damage (SDI) were assessed. Data from 70 patients with rheumatoid arthritis who had completed MDHAQ during their routine medical care were used as controls to compare the results of Physical Function (FN) domain exploratory factor analysis. Internal consistency reliability (ICR) for FN items was calculated using Cronbach's α. Validity of MDHAQ/RAPID3 was evaluated for content validity and construct validity. Responsiveness of the RAPID3 to changes in disease activity anchors was assessed. RESULTS: The ICR of the 10 physical function items on Cronbach's α was 0.88. Exploratory factor analysis revealed cross-loadings of three FN items. RAPID3 showed a strong correlation with LupusPRO health-related quality of life score (rho -0.68 (p < 0.001)), indicating convergent validity. RAPID3 scores did not correlate with disease activity indices or SDI. After adjustment for fibromyalgia status, a weak correlation with the Physician's Global Assessment (PGA) (rho = 0.31, p = 0.008) was noted. RAPID3 could differentiate between SLE patients based on flare status. RAPID3 was not responsive to changes in PGA, SELENA-SLEDAI or SELENA-Flare Index. CONCLUSIONS: MDHAQ/RAPID3 has fair reliability and validity in SLE.

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

Disease-specific quality of life in patients with lupus nephritis.

Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.

Developing a set of consensus indicators to support maternity service quality improvement: using Core Outcome Set methodology including a Delphi process.

OBJECTIVE: To develop a core metric set to monitor the quality of maternity care. DESIGN: Delphi process followed by a face-to-face consensus meeting. SETTING: English maternity units. POPULATION: Three representative expert panels: service designers, providers and users. MAIN OUTCOME MEASURES: Maternity care metrics judged important by participants. METHODS: Participants were asked to complete a two-phase Delphi process, scoring metrics from existing local maternity dashboards. A consensus meeting discussed the results and re-scored the metrics. RESULTS: In all, 125 distinct metrics across six domains were identified from existing dashboards. Following the consensus meeting, 14 metrics met the inclusion criteria for the final core set: smoking rate at booking; rate of birth without intervention; caesarean section delivery rate in Robson group 1 women; caesarean section delivery rate in Robson group 2 women; caesarean section delivery rate in Robson group 5 women; third- and fourth-degree tear rate among women delivering vaginally; rate of postpartum haemorrhage of ≥1500 ml; rate of successful vaginal birth after a single previous caesarean section; smoking rate at delivery; proportion of babies born at term with an Apgar score <7 at 5 minutes; proportion of babies born at term admitted to the neonatal intensive care unit; proportion of babies readmitted to hospital at <30 days of age; breastfeeding initiation rate; and breastfeeding rate at 6-8 weeks. CONCLUSIONS: Core outcome set methodology can be used to incorporate the views of key stakeholders in developing a core metric set to monitor the quality of care in maternity units, thus enabling improvement. TWEETABLE ABSTRACT: Achieving consensus on core metrics for monitoring the quality of maternity care.