We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Vitamin D deficiency is highly prevalent in the UK (1-2). Low exposure to the sun in winter months, as well as higher risk of deficiency amongst some ethnic minority populations (1), means that fortification of food and beverages remains an important potential route to ensure optimal vitamin D status. However, it is unclear as to whether type of fortified food affects ability to raise vitamin D status. Animal foods (e.g. dairy foods) would be expected to lead to higher vitamin D absorption than would non-animal-based foods (e.g. bread, juice), due to their higher fat content. The primary aim of this systematic review and meta-analysis was to investigate the effectiveness of animal and non-animal-based vitamin D fortified foods on raising serum 25-hydroxyvitamin D (25(OH)D).
The literature search was conducted using PubMed on 23 January 2024. Inclusion criteria were as follows: data on non-pregnant/non-lactating adults or data on children, randomised controlled trial; data for 25(OH)D measurement. Initial search results retrieved 701 publications, and 593 ineligible records were removed. Next, 108 records were screened by title and abstract, with 63 records excluded, for the following reasons: off topic (n=54); pregnant or breastfeeding (n=6); non-human (n=1); preterm infants (n=1) and duration <4 weeks (n=1). After full text eligibility screening, 28 publications remained for systematic review and meta-analysis. Ethical approval was not required as this was a literature review.
The end point data meta-analysis showed (for all studies combined) a significant increase in 25(OH)D (+23.4 (95% CI 17.0, 29.7) nmol/L (24 studies)). For specific food types, results were as follows: ‘animal’ +21.7 (95% CI 14.1, 29.3) nmol/L (17 studies); mixture of ‘animal’ and ‘non-animal’ +26.1 (95% CI 10.8, 41.4) nmol/L (1 study); ‘non-animal’ +28.1 (95% 12.0, 44.2) nmol/L (6 studies).
Contrary to what would be expected, non-animal mode of fortification (e.g. bread, juice) had a similar effect size to animal modes (e.g. dairy), so can be considered equivalent in effectiveness in raising 25(OH)D concentration. Differences in dose, duration and population groups between the non-animal and animal modes (in terms of health and baseline vitamin D status) mean the results should be taken with caution, and future studies where these factors are standardised could be useful to provide further evidence of effectiveness.
Malacological surveys were conducted in 2021 in the Kimpese region of Central Kongo Province, west of the Democratic Republic of Congo (DRC). Snail specimens were collected following a standardised protocol, identified using morphological and molecular methods, and tested for schistosome infection using a diagnostic PCR assay. Positive snail samples were sequenced to characterise the infecting schistosome species. Partial mitochondrial cytochrome c oxidase subunit 1 (COX1) gene sequences were used in phylogenetic analyses to explore the evolutionary position of these snail species within the broader African context. At least four intermediate snail hosts were identified: Bulinus truncatus, Bulinus forskalii, Biomphalaria pfeifferi, and a Biomphalaria species belonging to the Nilotic species complex (tentatively named Biomphalaria cf sudanica), of which the species identity needs to be confirmed. A total of 37 out of 1,196 snails (3.1%) tested positive for schistosome infection, with an infection prevalence of 7.4% for B. truncatus with Schistosoma haematobium and 1.5% for Biomphalaria spp. with Schistosoma mansoni. The S. mansoni sequence retrieved from these samples formed a basal clade relative to Zambian isolates, whereas S. haematobium grouped with the most frequently characterised haplotype cluster previously identified across mainland Africa. It is important to note that no animal schistosome species were identified in this study. Both the sequences from the snail hosts and the parasites represent novel contributions from the DRC. Additionally, the findings update the current knowledge of schistosomiasis transmission in the Kimpese region by providing insight into the phylogenetic placement, species diversity, and infection status of local snail populations.
The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.
Food security constitutes a worldwide concern closely correlated with population growth. By 2050, the global population is expected to reach 9.3 billion(1). The rising population, along with increasing life expectancy and shifts toward Western dietary patterns, is expected to drive higher food demand and contribute to a rise in metabolic conditions(2). In this context, looking for alternative and sustainable food and protein sources is imperative. Pasture legumes including lucerne (Medicago sativa) and red clover (Trifolium pratense) are becoming popular as they can be used as an alternative protein and functional food source. Both crops play an important role in New Zealand’s agriculture. Their seeds can be used in human nutrition as alternative food and protein options; however, the presence of anti-nutritional factors (ANF) and their distinct taste make them less favourable for human consumption. Fermentation can be used as a possible strategy to mitigate these limitations. Lactobacillus fermentation was conducted using Lactocillus plantarum, Lactobacillus. acidophilus and Lactobacillus. casei. Proximate composition and mineral content were determined following Association of Official Analytical Chemists (AOAC) methods. Total phenol content (TPC), total flavonoid content (TFC) and antioxidant activity (2,2-Diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) and ANF including phytic acid, trypsin, and chymotrypsin inhibition were assessed using colourimetric techniques. For the enzyme inhibition assays, enzyme-substrate reactions were performed with sample extracts before measurement. All the experiments were replicated three times, and the results were expressed as mean ± SD. A factorial analysis of variance (ANOVA) was conducted (4 legume seed samples × 3 LAB cultures) with a Tukey’s post-hoc test for mean comparison at P < 0.05 using IBM SPSS Statistics 29.0. All the legume seeds demonstrated high nutritional content, with crude protein and fibre levels around 40 and 16% respectively. The seeds were also rich in minerals, particularly magnesium, phosphorus, iron and zinc. In addition, fermentation led to an increase (P < 0.05) in TPC, TFC and antioxidant activity, while significantly reducing ANF. For instance, fermentation led to an increase in TPC (18.8 to 47.1% increase), TFC (9.6 to 34.5% increase) and AOA via DPPH and ABTS. Lactobacillus fermentation has proven to be an effective processing technique to enhance the nutritional value of lucerne and red clover seeds. These findings support the potential of using fermentation to develop novel and sustainable protein sources, contributing to improved dietary quality and nutrition. Moreover, further work to study the effect of fermentation on the nutrient digestibility of lucerne and red clover seeds is warranted.
New Zealand and Australian governments rely heavily on voluntary industry initiatives to improve population nutrition, such as voluntary front-of-pack nutrition labelling (Health Star Rating [HSR]), industry-led food advertising standards, and optional food reformulation programmes. Research in both countries has shown that food companies vary considerably in their policies and practices on nutrition(1). We aimed to determine if a tailored nutrition support programme for food companies improved their nutrition policies and practices compared with control companies who were not offered the programme. REFORM was a 24-month, two-country, cluster-randomised controlled trial. 132 major packaged food/drink manufacturers (n=96) and fast-food companies (n=36) were randomly assigned (2:1 ratio) to receive a 12-month tailored support programme or to the control group (no intervention). The intervention group was offered a programme designed and delivered by public health academics comprising regular meetings, tailored company reports, and recommendations and resources to improve product composition (e.g., reducing nutrients of concern through reformulation), nutrition labelling (e.g., adoption of HSR labels), marketing to children (reducing the exposure of children to unhealthy products and brands) and improved nutrition policy and corporate sustainability reporting. The primary outcome was the nutrient profile (measured using HSR) of company food and drink products at 24 months. Secondary outcomes were the nutrient content (energy, sodium, total sugar, and saturated fat) of company products, display of HSR labels on packaged products, company nutrition-related policies and commitments, and engagement with the intervention. Eighty-eight eligible intervention companies (9,235 products at baseline) were invited to participate, of whom 21 accepted and were enrolled in the REFORM programme (delivered between September 2021 and December 2022). Forty-four companies (3,551 products at baseline) were randomised to the control arm. At 24 months, the model-adjusted mean HSR of intervention company products was 2.58 compared to 2.68 for control companies, with no significant difference between groups (mean difference -0.10, 95% CI -0.40 to 0.21, p-value 0.53). A per protocol analysis of intervention companies who enrolled in the programme compared to control companies with no major protocol violation also found no significant difference (2.93 vs 2.64, mean difference 0.29, 95% CI -0.13 to 0.72, p-value 0.18). We found no significant differences between the intervention and control groups in any secondary outcome, except in total sugar (g/100g) where the sugar content of intervention company products was higher than that of control companies (12.32 vs 6.98, mean difference 5.34, 95% CI 1.73 to 8.96, p-value 0.004). The per-protocol analysis for sugar did not show a significant difference (10.47 vs 7.44, mean difference 3.03, 95% CI -0.48 to 6.53, p-value 0.09).In conclusion, a 12-month tailored nutrition support for food companies did not improve the nutrient profile of company products.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
A Rank Forum was convened to discuss the evidence around food insecurity (FIS), its impact on health, and interventions which could make a difference both at individual and societal level, with a focus on the UK. This paper summarises the proceedings and recommendations. Speakers highlighted the growing issue of FIS due to current economic and social pressures. The health implications of FIS vary geographically since food insecure women in higher income regions tend to be living with overweight or obesity, in contrast to those living in low-to-middle-income countries. This paradox could be due to stress and/or metabolic or behavioural responses to an unpredictable food supply. The gut microbiota may play a role given the negative effects of low fibre diets on bacterial diversity. Solutions to FIS involve individual behavioural change, targeted services and societal/policy change. Obesity-related services are currently difficult to access. Whilst poverty is the root cause of FIS, it cannot be solved solely by making healthy food cheaper due to ingrained beliefs, attitudes and behaviours in target groups. Person-centred models, such as Capability-Opportunity-Motivation Behavioural Change Techniques and Elicit-Provide-Elicit communication techniques, are recommended. Societal change or improved resilience through psychological support may be more equitable ways to address FIS. They can combine with fiscal or food environment policies to shift purchasing towards healthier foods. Policy implementation can be slow to enact due to the need for strong evidence, consultation and political will. Eradicating FIS must involve co-creation of interventions and policies to ensure a consensus on solutions.
Background: Nipocalimab (a fully human, effectorless anti-neonatal Fc receptor (FcRn) monoclonal antibody) may ameliorate gMG disease manifestations by selectively targeting FcRn IgG recycling and lowering IgG, including pathogenic autoantibodies in generalized myasthenia gravis (gMG). The objective was to evaluate the effectiveness and safety of intravenous nipocalimab added to background standard-of-care therapy in adolescents with gMG. Methods: Seropositive patients (12-<18 years) with gMG (MGFA Class II-IV) on stable therapy but inadequately controlled, were enrolled in a 24-week open label study. Nipocalimab was administered as a 30 mg/kg IV loading dose followed by 15 mg/kg IV every 2 Weeks. Results: Seven adolescents were enrolled; 5 completed 24-weeks of dosing. The mean(SD) age was 14.1(1.86) years; seven were anti-AChR+, six were female. Mean(SD) baseline MG-ADL/QMG scores were 4.29(2.430)/12.50(3.708). Nipocalimab showed a significant reduction in total serum IgG at week-24; the mean(SD) change from baseline to week-24 for total serum IgG was -68.98%(7.561). The mean(SD) change in MG-ADL/QMG scores at week-24 was -2.40(0.418)/-3.80(2.683); 4 of 5 patients achieved minimum symptom expression (MG-ADL score 0-1) by week-24. Nipocalimab was well-tolerated; there were no serious adverse events. There were no clinically meaningful laboratory changes. Conclusions: Nipocalimab demonstrated efficacy and safety in this 6-month trial in seropositive adolescents with gMG.
Background: Autonomic nervous system (ANS) dysfunction in people with epilepsy (PwE) is a likely contributor to sudden unexpected death in epilepsy (SUDEP). However, the nature of autonomic dysfunction among PwE remains poorly understood. We aimed to delineate self-reported ANS functioning among people with drug-resistant epilepsy, a patient group at increased risk for SUDEP. Methods: People with focal drug-resistant epilepsy undergoing stereoelectroencephalography at the Epilepsy Monitoring Unit in London, Ontario completed the Composite Autonomic Symptom Score (COMPASS-31), a widely used questionnaire for ANS function. Results: The mean total COMPASS-31 score (N=34; 13 females) was 27.36 (SD=13.77). There was no significant correlation between total COMPASS-31 score and current age (mean=32.71 years, SD=10.58; r(32)= -0.04) or age of epilepsy onset (mean=17.31 years, SD=8.26; r(30)=0). Females scored higher than males (t(32)=3.41, p<.05), but scores did not differ between participants with an epileptogenic zone in the temporal lobe(s) (N=20) and participants with multi-focal, extra-temporal or unknown epileptogenic zones (t(32)=0.18). Participants prescribed 2-3 sodium channel blocking anti-seizure medications (cardiotoxic; N=17), scored worse than participants on 0-1 sodium channel blockers (N=17) (t(32)= -2.15, p<.05). Conclusions: Autonomic testing should be a standard component of clinical care for people with drug-resistant epilepsy, especially for females and for those on sodium channel blockers.
Background: Vestibular schwannoma (VS) are the most common tumour of the CPA with an annual incidence of 17.4/1 million. They typically demonstrate slow growth over time and as such, observation is a reasonable approach to management. A portion of these tumour remain static and approximately 5-10% of these tumours will demonstrate spontaneous regression while under observation, including those associated with neurofibromatosis type-2.
Previous case series (N= 13-14) have attempted to identify predictive factors for tumour growth and regression, but few have reached significance or demonstrated reproducible findings. Methods: Using a clinical database of VS treated by one team at our institution, we identified 40 patients who have demonstrated significant spontaneous regression or complete resolution of their VS. All patients received a survey by mail and telephone. Results: Radiographic descriptions were collected on 40 patients. Surveys were completed by 18 participants and an additional 18 control patients who demonstrated growth and underwent surgical resection. Conclusions: This is the largest case series we know of to date describing radiographic and clinical presentations of patients shrinking vestibular schwannoma. It is also the only study known to date to consider patient factors by survey in an attempt to identify protective factors.
Background: Neurofibromatosis 1 (NF1) is a multisystem neurocutaneous disorder. Treatment involves multiple specialists. There are currently no multidisciplinary clinics for adults with NF1 in BC, which impacts communication between subspecialties. We sought perspectives of patients and providers to identify the impact of and solutions to gaps in care. Methods: Focus groups with patients (2 groups; 9 patients) and physicians (10) who see people with NF1 were conducted. Thematic content analysis was applied to the data to derive major themes. Concurrently, quarterly NF multidisciplinary rounds were initiated to enhance coordination of care. Results: Major themes emerged around the need for increased coordination and communication amongst providers. Specifically, physicians identified working in “siloed care structures”, and patients and providers identified lack of awareness of expertise and barriers to accessing care. Conclusions: Focus groups enable inclusion of patient and provider perspectives in developing solutions to gaps in care. The importance of supporting interdisciplinary communication in caring for NF1 patients was confirmed in focus groups. To date, we have held multidisciplinary NF rounds, with 12 cases discussed. Disciplines represented include neurology, pediatrics, radiology, neuro-ophthalmology, neuro-otology, pathology, orthopedic plastic and neurosurgery, medical and radiation oncology, and the hereditary cancer program. Telehealth format enables participation from distributed centres across BC.
Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.
Background: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.
Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.