Inconsistent Evidence Research Articles

Multi-Organ Phenotypes of Offspring Born Following Hypertensive Disorders of Pregnancy: A Systematic Review.

Hypertensive pregnancies are associated with an increased risk of cardiovascular and neurological diseases in the offspring during later life. However, less is known about the potential impact on multi-organ phenotypes in offspring before disease symptoms occur. The objective of this systematic review was to determine the associations of fetal exposure to maternal hypertensive pregnancy with multi-organ phenotypes across developmental stages. Ovid MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), WoS, Scopus, CINAHL, and ClinicalTrials.gov were systematically searched until February 2024. Records were independently screened by 2 authors. Studies reporting on the structure or function of the heart, blood vessels, brain, liver, and kidneys in offspring of hypertensive pregnancies compared with a normotensive control population were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Extracted data were presented using harvest plots. Seventy-three studies including 7091 offspring of hypertensive pregnancies and 42 164 controls were identified that met the inclusion criteria. Thirty-two studies were investigations in fetuses, 24 in neonates and infants, 12 in children, 2 in adolescents, and 3 in adults. Offspring of hypertensive pregnancies had structural and functional changes in the heart compared with controls in some studies across developmental stages. Offspring of hypertensive pregnancies also had smaller occipital and parietal vessels, higher aortic intima-media thickness, and lower retinal arteriolar-to-venular ratio. Some conflicting evidence existed for other phenotypical alterations. There is still inconsistent evidence of multi-organ structural and functional differences in offspring of hypertensive pregnancies. The evidence base could therefore be further strengthened through well-designed and conducted prospective studies. www.crd.york.ac.uk. Unique Identifier: CRD42023387550.

Relationship between Muscle Mass and Muscle Strength with Bone Density in Older Adults: A Systematic Review.

Understanding the relationship between muscle mass, muscle strength, and bone density in older adults is crucial for addressing age-related conditions like osteoporosis and sarcopenia. This review aims to evaluate the relationship between muscle mass and muscle strength with bone density in older adults. This systematic review, following PRISMA guidelines, involved a comprehensive search across seven databases from 2014 to April 2024. Included were observational studies in English and Indonesian on adults aged 60 and older. The AXIS tool assessed the risk of bias, and the GRADE framework evaluated the evidence quality. Study selection was independently reviewed, and consensus was reached through discussion. Ten studies were included. For muscle mass and bone density, five studies showed a significant association, while four did not. For muscle strength and bone density, four of seven studies reported a significant association. However, the evidence quality was low due to inconsistency. The relationship between muscle mass, muscle strength, and bone density in older adults shows variability and inconsistent evidence.

Serum sodium concentration predicting mortality in patients with aneurysmal subarachnoid hemorrhage

BackgroundTo date, inconsistent evidence exists on the role of hypernatremia in patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent surgical clipping. We aimed to investigate the association between serum sodium and mortality in these patients. MethodsA cohort study was performed to include adult patients with aSAH who underwent surgical clipping in a university hospital. The primary outcome was follow-up mortality. Propensity score matching (PSM) was used for matching patients’ baseline characteristics. Net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess and compare the reclassification and discrimination capacity of different models. Trends in serum sodium over time were detected by the ordinary least squares model. ResultsOf 618 aSAH patients with surgical clipping during the study period, normal serum sodium was observed in 467 patients (75.6 %), and admission hypernatremia was noted in 151 patients (24.4 %). After adjustment with multivariate regression analysis, patients with hypernatremia had significantly higher odds for follow-up mortality (aOR: 2.86, 95 % CI: 1.54 to 5.30; P = 0.001). PSM analysis observed similar results (aOR: 2.38, 95 % CI: 1.29 to 4.55; P = 0.009). The incorporation of serum sodium during hospitalization markedly enhanced the IDI (P < 0.001) and NRI (P < 0.001) for the prediction of mortality. ConclusionsIn conclusion, the findings from this cohort study of aSAH patients with surgical clipping indicated that serum sodium can be an independent predictive factor of all-cause mortality, and inferior sequelae in aSAH patients. These findings endorsed the importance of managing hypernatremia and monitoring serum sodium in patients with aSAH.

Methylation Mesa define functional regulatory elements for targeted gene activation.

DNA methylation and mRNA expression correlations are often presented with inconsistent evidence supporting causal regulation. We hypothesized that causal regulatory methylation elements would exhibit heightened demethylation sensitivity. To investigate, we analyzed 20 whole genomic bisulfite sequenced samples before and after demethylation and identified narrow width (45 294 bp) elements within a short plateau, termed Methylation Mesa (MM). The Mesa signature was conserved across species and was independent of CpG islands. Mesa also demonstrate high concordance with primed and active histone marks. To assess causality, we developed CRISPR DiR, a highly precise targeted demethylation technology. Targeted demethylation of a Mesa triggers locus and distal chromatin rewiring events that initiate mRNA expression significantly greater than promoter CpG island targeting. Thus, Mesa are self-sustaining epigenetic regulatory elements that maintain long-term gene activation through focused demethylation only within the Mesa core, resulting in subsequent histone modifications and chromatin rewiring events that interact with distal elements also marked as Mesas.

The association between atopic dermatitis and linear growth in children- a systematic review.

To evaluate the association between atopic dermatitis (AD) and linear growth in children, and determine factors associated with compromised linear growth in children with AD. A PRISMA-compliant systematic review was conducted. Databases (PubMed, Embase, Scopus and Cochrane) were searched from inception to June 2024 for articles that reported a quantitative relationship between AD and linear growth in children (< 18years old). Quality of included articles was assessed using the Joanna Briggs Institute Critical Appraisal Tools while quality of evidence in these studies was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Fourteen studies (comprising 50,146 patients with AD) were included. Seven studies reported a strong positive or positive association between AD and reduced height standard deviation score (SDS) in children; the others reported no association. Only 3 studies had moderate quality of evidence, all of which reported an association between AD and poorer height SDS; the remaining 11 studies scored low in quality of evidence. Three studies reported the impact of AD on height to be transient. Secondary analysis showed AD severity, earlier AD onset, sleep disruption and, food restriction, to be risk factors for linear growth impairment in patients with AD. Topical steroid use was not associated with shorter stature in patients with AD. Conclusion: Current evidence on the association between childhood AD and poor linear growth is weak and inconsistent. However, patients with more severe AD, earlier disease onset, poorer sleep quality and higher nutritional restrictions appear more susceptible to linear growth impairment. What is known? • There is inconsistent evidence of the association between atopic dermatitis (AD) and linear growth in children in current literature, with some studies suggesting that AD may negatively impact linear height while other studies do not report similar associations. What is new? • There is no strong association between AD in childhood and poorer linear growth. • There may be a transient slowing of linear growth in children with AD, mimicking constitutional growth delay. • Children with severe AD, earlier disease onset, poorer sleep quality and nutritional restrictions may be at risk of more significant linear growth impairment. • Topical steroid use does not appear to contribute to shorter height in children with AD.

Autoimmunity’s enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complicated, heterogeneous condition distinguished by post-exertional neuroimmune exhaustion and multisystem symptoms. Its complexity poses challenges for physicians, researchers and those inflicted by its presence. Due to conflicting evidence and limiting consensus, the association and contribution autoimmunity serves in the pathophysiology or aetiology of ME/CFS is yet to be confirmed. This systematic review synthesises the currently available data to clarify the role autoimmunity has in the pathogenesis of ME/CFS and explore the therapeutic limitations.MethodsThis systematic review was conducted in accordance with the PRISMA and Cochrane guidelines. Full-text articles containing the primary key terms “Autoimmunity/Autoimmune” and “ME/CFS” were included provided their suitability to the inclusion and exclusion criteria.ResultsTen publications investigating the role of autoimmunity in ME/CFS were examined. One investigated the role of cytokine signalling; Three investigated the genetic nature of autoimmunity in ME/CFS patients; One examined the immune lineage of ME/CFS patients; Six investigated the presence and role of autoantibodies in ME/CFS patients.ConclusionThe findings generated from this systematic review highlight inconsistent and insufficient evidence to classify ME/CFS as an autoimmune disease. Additionally, it further emphasises the complexity of ME/CFS and highlights the challenges in distinguishing autoreactivity from deregulatory processes. Future research is urgently needed to advance the development of diagnostic and treatment strategies.PROSPERO Registration CodeCRD42024533447.

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

General Obesity and Prostate Cancer in Relation to Abdominal Obesity and Ethnic Groups: A US Population-Based Cross-Sectional Study.

Research suggests inconsistent evidence regarding the association between general obesity and prostate cancer among men in the United States. This study aimed to examine whether the association between general obesity and prostate cancer is influenced by abdominal obesity and ethnic groups. The study utilized data from the National Health and Nutrition Examination Survey (NHANES). The analysis was restricted to non-Hispanic men (10,683 White and 6,020 Black). Obesity was defined as body mass index (BMI) ≥30 and abdominal obesity as waist circumference (WC) ≥102 cm. No significant difference was identified in the overall prevalence of prostate cancer between obese and non-obese (2.14% vs 2.25%, P = 0.678). When both obesity measures were combined, the general and abdominal obesity category was associated with a significant increase in the odds of prostate cancer in Black men [odds ratio (OR) = 1.49, 95% confidence interval (CI) (1.09, 2.04)], but not in White men [OR = 1.29, 95% CI (0.91, 1.82)]. In both Black [OR = 2.46, 95% CI (1.48, 4.06)] and White men [OR = 1.60, 95% CI (1.16, 2.21)], abdominal obesity was associated with significant increase in the odds of prostate cancer. The association between general obesity and prevalence of prostate cancer depends on abdominal obesity and ethnic groups. Our study utilized a nationally representative survey and emphasized the potential of combined effect of general and abdominal obesity as a modifiable factor to decrease racial disparity in prostate cancer screening and poor outcomes.

Investigating the Potential Short-term Adverse Effects of the Quadrivalent Human Papillomavirus Vaccine: A Novel Regression Discontinuity Analysis

Background: Human papillomavirus (HPV) vaccination has been offered in over a hundred countries worldwide (including the United Kingdom, since September 2008). Controversy around adverse effects persists, with inconsistent evidence from follow-up of randomized controlled trials and confounding by indication limiting the conclusions drawn from larger-scale observational studies. This study aims to estimate the association between receiving a quadrivalent HPV vaccine and the reporting of short-term adverse effects and to demonstrate the utility of regression discontinuity design for examining side effects in routine data. Methods: We applied a novel regression discontinuity approach to a retrospective population-based cohort using primary care data from the UK Clinical Practice Research Datalink linked to hospital and social deprivation data. We examined the new onset of gastrointestinal, neuromuscular, pain, and headache/migraine symptoms using READ and International Classification of Diseases, tenth revision diagnostic codes. For each year between 2012 and 2017, we compared girls in school year 8 (born July/August) who were eligible to receive the vaccine with girls in year 7 (born September/October) who were not eligible. Results: Of the 21,853 adolescent girls in the cohort, 10,881 (50%) were eligible for HPV vaccination. There was no evidence of increased new gastrointestinal symptoms (adjusted odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.85, 1.15), headache/migraine symptoms (OR: 0.84; 95% CI: 0.70, 1.01), or pain symptoms (OR: 1.05; 95% CI: 0.95, 1.16) when comparing those eligible and ineligible for HPV vaccination. Conclusion: This study found no evidence that HPV vaccination eligibility is associated with reporting short-term adverse effects among adolescent girls.

Prognostic Factors and Changes in Pain, Physical Functioning, and Participation in Patients With Hip and/or Knee Osteoarthritis: A Systematic Review.

This study aimed to systematically synthesize literature on prognostic factors of changes in either direction (ie, worsening or improvement) in pain, physical functioning, and participation in patients with knee and/or hip osteoarthritis (OA). Studies included in two preceding reviews underwent full-text screening for inclusion in the current review. Additionally, an extensive literature search was conducted in five databases. Title/abstract screening was performed using an active learning program. Inclusion criteria comprised patients diagnosed with knee and/or hip OA, with the dependent variable assessing pain, physical functioning, or participation. Potential associated prognostic factors were measured as independent variables. The methodologic quality of studies was assessed with the Hayden criteria. A total of 31 studies were included in this systematic review. In patients with knee OA, pain worsening was associated with lower physical functioning (strong evidence) and with higher body mass index, ethnicity, and a higher comorbidity count (moderate evidence). Also, in patients with knee OA, pain improvement was associated with less pain at baseline (moderate evidence). In patients with knee and/or hip OA, worsening of physical functioning exhibited associations with higher body mass index, more pain, more hip pain, a higher comorbidity count, higher avoidance of activities (strong evidence), and ethnicity (moderate evidence). In patients with knee OA, improvement in physical functioning showed an association with higher vitality (moderate evidence). Regarding the remaining prognostic factors, there is weak, inconclusive, or inconsistent evidence for an association with the outcomes. In patients with hip OA, only weak evidence was found for three factors predicting a change in physical functioning. This review encompasses prognostic factors associated with changes in either direction (ie, worsening or improvement) in pain, physical functioning, and participation. The results are consistent with other reviews. Future research should place a stronger emphasis on patients with hip OA and participation as an outcome.

The Association Between Maternal ABO Blood Group and the Occurrence of Spontaneous Preterm Birth: A Retrospective Population-Based Cohort Study.

There is limited and inconsistent evidence that imply a relationship between ABO blood types and rate of preterm birth (PTB). We aim to examine the association between maternal ABO blood group and PTB rate. A retrospective-study conducted at a university teaching institution on data collected between 2013 and 2019. Women who delivered a viable neonate at ≥ 24 weeks without major malformations were included. Indicated PTBs were excluded. PTB and early PTB were defined as deliveries that occurred < 37 and < 34 weeks respectively. PTB was further divided into 3 subgroups according to etiology: membranes rupture, intact membranes, and placental abruption regardless of membranes' status. The primary outcome was spontaneous PTB rate. Of 19,301 women included, PTB and early PTB rates were 7.3% (1,418/19,301) and 2.3% (440/19,301) respectively. Rates of PTB in blood groups A, B, O, and AB, were 7.3%, 6.9%, 7.5%, and 7.5% respectively (p = 0.68). There was no significant difference according to etiology. Rates of early PTB were also comparable (p = 0.63). After adjustment for demographic and obstetric variables, blood type was associated with increased placental abruption rate among women who had early PTB (p = 0.038). Placental abruption rate was significantly higher in group A (22.5%) compared to group B (14.1%), (adjusted p = 0.04) and group O (14.0%), (adjusted p = 0.01). The rate in group AB was 17.1%, (adjusted p = 0.85). In conclusion, no association was found between a particular blood group and PTB rate. Women with group A, admitted in early PTB, had an increased risk that the underlying etiology was placental abruption.

Hyperarousal dynamics reveal an overnight increase boosted by insomnia

Hyperarousal is a key symptom of anxiety, stress-related disorders, and insomnia. However, it has been conceptualized in many different ways, ranging from various physiological markers (e.g. cortisol levels, high-frequency EEG activity) to personality traits, or state assessments of subjective anxiety and tension. This approach resulted in partly inconsistent evidence, complicating unified interpretations. Crucially, no previous studies addressed the likely variability of hyperarousal within and across days, nor the relationship of such variability in hyperarousal with the night-by-night variability in sleep quality characteristic of insomnia.Here, we present a novel data-driven approach to understanding dynamics of state hyperarousal in insomnia. Using ecological momentary assessment, we tracked fluctuations in a wide range of emotions across 9 days in 169 people with insomnia disorders and 38 controls without sleep problems. Exploratory factor analysis identified a hyperarousal factor, comprised of items describing tension and distress. People with insomnia scored significantly higher on this factor than controls at all timepoints. In both groups, the hyperarousal factor score peaked in the morning and waned throughout the day, pointing to a potential contributing role of sleep or other circadian processes. Importantly, the overnight increase in hyperarousal was stronger in people with in insomnia than in controls. Subsequent adaptive LASSO regression analysis revealed a stronger overnight increase in hyperarousal across nights of worse subjective sleep quality.These findings demonstrate the relationship between subjective sleep quality and overnight modulations of hyperarousal. Disorders in which hyperarousal is a predominant complaint might therefore benefit from interventions focused on improving sleep quality.

Determinants of Multilevel Discourse Outcomes in Anomia Treatment for Aphasia.

Individuals with aphasia identify discourse-level communication (i.e., language in use) as a high priority for treatment. The central premise of most aphasia treatments is that restoring language at the phoneme, word, and/or sentence level will generalize to discourse. However, treatment-related changes in discourse-level communication are modest, are poorly understood, and vary greatly among individuals with aphasia. In response, this study consisted of a multilevel discourse analysis of archival, monologic discourse outcomes across two high-intensity Semantic Feature Analysis (SFA) clinical trials. Aim 1 evaluated changes in theoretically motivated discourse outcomes representing lexical-semantic processing, lexical diversity, grammatical complexity, and discourse informativeness. Aim 2 explored the potential moderating role of nonlanguage cognitive factors (semantic memory, divided attention, and executive function) on discourse outcomes. This study was a retrospective analysis of archival monologic discourse outcomes after intensive SFA for n = 60 (Aim 1) and a subset n = 44 (Aim 2). Outcome measures included lexical-semantic processing (% semantic errors), lexical diversity (moving average type-token ratio), grammatical complexity (mean utterance length), and discourse informativeness (% correct information units). Bayesian generalized mixed-effects models were used to examine changes across four study time points: enrollment, entry, exit, and 1-month follow-up. The present study found no evidence for meaningful or statistically reliable improvements in monologue discourse performance after SFA when measured using standard, general-topic discourse stimuli. There was weak and inconsistent evidence that nonlanguage cognitive factors may play a role in moderating treatment response. These findings indicate a clear need to pair theoretically informed treatments designed to facilitate generalization to discourse with intentional measurement paradigms designed to capture it. Furthermore, there is a clear need to examine how established treatments, restorative or compensatory, can better facilitate generalization to discourse-level communication. These priorities are critical for meaningfully improving everyday communication and reducing the profound communication and psychosocial consequences of aphasia. https://doi.org/10.23641/asha.26524081.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood bone mineral density: A prospective birth cohort study

Background and aimPerfluoroalkyl and polyfluoroalkyl substances (PFAS) have demonstrated potential toxicity in skeletal development. However, the relationship between prenatal PFAS exposure and offspring bone health remains unclear in epidemiological studies. Therefore, we aim to investigate whether prenatal exposure to PFAS is associated with bone mineral density (BMD) in offspring. MethodThis study population included 182 mother-child pairs in the Shanghai Obesity and Allergy Cohort, enrolled during 2012–2013. 10 PFAS were measured by liquid chromatography-mass spectrometry (LC-MS) in cord plasma. The child's spinal BMD was measured using a dual-energy X-ray absorptiometry (DXA) scanner at the age of 8. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into quartiles) and child BMD. Bayesian kernel machine regression (BKMR) was employed to explore the joint effects of PFAS mixtures on BMD. ResultsAmong the 10 PFAS, 8 of them had a detection rate >90% and were included in the subsequent analysis. We observed no significant associations between individual PFAS (as a continuous variable) and spinal BMD in 8-year-old children using the multivariable linear regression model. When treated as quartile categories, the second and fourth quartiles of perfluorobutane sulfonate (PFBS) was associated with higher BMD in the first lumbar vertebra, compared with the lowest quartile. BKMR analysis revealed no association between the PFAS mixture and child BMD. ConclusionWe observed no associations of prenatal PFAS exposure with child BMD at 8 years of age. Given the inconsistent epidemiological evidence, further research is needed to confirm these findings from other studies or elucidate the potentially toxic effects of PFAS on bone.

Changes in the Firmicutes to Bacteriodetes ratio in the gut microbiome in individuals with anorexia nervosa following inpatient treatment: A systematic review and a case series.

Anorexia nervosa has the highest mortality rate among psychiatric illnesses. Current treatments remain ineffective for a large fraction of patients. This may be due to unclear mechanisms behind its development and maintenance. Studies exploring the role of the gut microbiome have revealed inconsistent evidence of dysbiosis. This article aims to investigate changes in the gut microbiome, particularly, mean differences in the Firmicutes to Bacteroidetes ratio, in adolescent and adult individuals with anorexia nervosa following inpatient treatment. Longitudinal studies investigating gut microbiome composition in inpatient populations of anorexia nervosa before and after treatment were systematically reviewed. Additionally, gut microbiome compositions were characterized in three acute anorexia nervosa inpatients early after admission and after 4-12weeks of treatment. Review results indicated an increase in the Firmicutes to Bacteroidetes ratio in individuals with anorexia nervosa after treatment. These however did not match values of their healthy counterparts. In the case-series samples, the reverse occurred with samples taken 4weeks after treatment. In the patient who provided an extra sample 12weeks after treatment, similar results to the studies included in the review were observed. Furthermore, Firmicutes to Bacteroidetes ratio values in the case-series samples were notably higher in the two patients who had chronic anorexia nervosa. Differences in methodologies, small sample sizes, and insufficient data limited the generalizability of the outcomes of the reviewed studies. Results suggest a potentially unique microbiome signature in individuals with chronic anorexia nervosa, which may explain different outcomes in this group of patients.

Comparative effectiveness and safety of direct oral anticoagulants and warfarin in atrial fibrillation patients with dementia.

Developing an effective stroke prevention strategy is crucial for elderly atrial fibrillation (AF) patients with dementia. This is due to the limited and inconsistent evidence available on this topic. In this nationwide, population-based cohort study, we aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in AF patients with dementia. We identified AF patients with dementia, aged 50 years or older, from Taiwan's National Health Insurance Research Database between 2010 and 2019. The primary outcome was a composite of hospitalizations due to ischemic stroke, acute myocardial infarction, intracranial hemorrhage, or major bleeding, as well as all-cause mortality. We used 1:1 propensity score matching and Cox proportional hazard models to adjust for confounding factors when comparing outcomes between warfarin and DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) users or warfarin and each individual DOAC. There were 2952 patients in the DOAC-warfarin matched cohort. The apixaban-, dabigatran-, edoxaban-, and rivaroxaban-warfarin matched cohorts had 2346, 2554, 1684, and 2938 patients, respectively. The DOAC group, when compared to warfarin, was associated with a lower risk of both the composite outcome (hazard ratio (HR), 0.81; 95% confidence interval (CI) 0.69-0.95) and ischemic stroke (HR 0.65; 95% CI 0.48-0.87). Apixaban (HR 0.79; 95% CI 0.66-0.94), dabigatran (HR 0.64; 95% CI 0.53-0.77), and rivaroxaban (HR 0.82; 95% CI 0.70-0.97) were also associated with a lower risk of the composite outcome. Compared to warfarin, DOACs, whether as a group or apixaban, dabigatran, or rivaroxaban individually, were associated with a reduced risk of the composite outcome in elderly patients with concurrent AF and dementia.

Resting-State Functional Connectivity of the Amygdala in Autism: A Preregistered Large-Scale Study.

Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This study addressed these limitations while testing the above three hypotheses, applied to amygdala functional connectivity. In a comprehensive preregistered study, the three hypotheses were tested in a subset (N=488 after exclusions; N=212 with ASD) of the Autism Brain Imaging Data Exchange data sets. The authors analyzed resting-state functional connectivity (FC) from functional MRI data from two anatomically defined amygdala subdivisions, in three hypotheses with respect to magnitude, pattern similarity, and variability, across different anatomical scales ranging from whole brain to specific regions and networks. A Bayesian approach to hypothesis evaluation produced inconsistent evidence in ASD for atypical amygdala FC magnitude, strong evidence that the multivariate pattern of FC was typical, and no consistent evidence of increased interindividual variability in FC. The results strongly depended on analytic choices, including preprocessing pipeline for the neuroimaging data, anatomical specificity, and subject exclusions. A preregistered set of analyses found no reliable evidence for atypical functional connectivity of the amygdala in autism, contrary to leading hypotheses. Future studies should test an expanded set of hypotheses across multiple processing pipelines, collect deeper data per individual, and include a greater diversity of participants to ensure robust generalizability of findings on amygdala FC in ASD.

Substance misuse by birth parents: Outcomes for children and young people placed into out-of-home-care

BackgroundThere is inconsistent evidence regarding the effect of birth parent substance use on developmental outcomes for children placed into out-of-home-care (OOHC). ObjectiveThis study aims to examine how parental substance use affects outcomes of Australian children in out-of-home care, adjusting for key demographic, social and system factors. Participants and settingFour waves of survey data were collected for children and young people who agreed to participate in the Pathways of Care Longitudinal Study (POCLS) between 2011 and 2018. The study sample included 1,506 children and young people (792 with a history of parental substance misuse) aged 9 months to 17 years who participated in at least one wave of the POCLS and had linked administrative data from the Department of Communities and Justice (DCJ), NSW, Australia. MethodsMultilevel longitudinal models were used to analyse the relationship of child developmental outcomes (physical health, socio-emotional wellbeing, and verbal and non-verbal cognitive ability) with parental substance misuse in their child protection history. Each model included adjustments for child demographics, family socio-economic status, child protection system factors and the unbalanced panel. ResultsChildren in OOHC with a history of parental substance misuse were more likely to be in the typical range for verbal cognitive development compared to those in OOHC without this history. In addition, younger (9 months to 5 years) children with a record of parental substance misuse exhibited significantly more typical fine and gross motor skill development than those without this history. ConclusionsConcerns that children in OOHC with a history of parental substance misuse may be more affected with regards to early-stage physical development, and later verbal cognitive development than those without this history in OOHC, may not be justified.

Dietary Supplementation on Physical Performance and Recovery in Active-Duty Military Personnel: A Systematic Review of Randomized and Quasi-Experimental Controlled Trials.

Warfighters, often called tactical athletes, seek dietary supplementation to enhance training and recovery. Roughly 69% of active-duty US military personnel have reported consuming dietary supplements. The objective of this systematic review was to examine the impact of dietary supplements on muscle-related physical performance and recovery in active-duty military personnel. Randomized controlled trials and quasi-experimental controlled trials of oral dietary supplementation in active-duty military members were examined. A protocol was registered (PROSPERO CRD42023401472), and a systematic search of MEDLINE and CINAHL was undertaken. Inclusion criteria consisted of studies published between 1990-2023 with outcomes of muscle performance and recovery among active-duty military populations. The risk of bias was assessed with the McMaster University Guidelines and Critical Review Form for Quantitative Studies. Sixteen studies were included. Four were conducted on protein or carbohydrate; four on beta-alanine alone, creatine alone, or in combination; two on mixed nutritional supplements; two on probiotics alone or in combination with beta hydroxy-beta methylbutyrate calcium; and four on phytonutrient extracts including oregano, beetroot juice, quercetin, and resveratrol. Ten examined outcomes related to physical performance, and six on outcomes of injury or recovery. Overall, protein, carbohydrate, beta-alanine, creatine, and beetroot juice modestly improved performance, while quercetin did not. Protein, carbohydrates, beta-alanine, probiotics, and oregano reduced markers of inflammation, while resveratrol did not. Nutrition supplementation may have small benefits on muscle performance and recovery in warfighters. However, there are significant limitations in interpretation due to the largely inconsistent evidence of ingredients and comparable outcomes. Thus, there is inadequate practical evidence to suggest how dietary supplementation may affect field performance.

Indigenous access to clinical services along the lung cancer treatment pathway: a review of current evidence.

Lung cancer is a deadly cancer. Early diagnosis and access to timely treatment are essential to maximizing the likelihood of survival. Indigenous peoples experience enduring disparities in lung cancer survival, and disparities in access to and through lung cancer services is one of the important drivers of these disparities. In this manuscript, we aimed to examine the current evidence on disparities in Indigenous access to services along the lung cancer treatment pathway. A narrative literature review was conducted for all manuscripts and reports published up until July 20, 2022, using Medline, Scopus, Embase, and Web of Science. Following the identification of eligible literature, full-text versions were scanned for relevance for inclusion in this review, and relevant information was extracted. After scanning 1,459 documents for inclusion, our final review included 36 manuscripts and reports that included information on lung cancer service access for Indigenous peoples relative to non-Indigenous peoples. These documents included data from Aotearoa New Zealand, Australia, Canada, and the USA (including Hawai'i). Our review found evidence of disparities in access to, and the journey through, lung cancer care for Indigenous peoples. Disparities were most obvious in access to early detection and surgery, with inconsistent evidence regarding other components of the pathway. These observations are made amid relatively scant data in a global sense, highlighting the need for improved data collection and monitoring of cancer care and outcomes for Indigenous peoples worldwide. Access to early detection and guideline-concordant treatment are essential to addressing enduring disparities in cancer survival experienced by Indigenous peoples globally.