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Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Annals of Oncology : Official Journal... Jan 2024The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI... (Review)
Review
BACKGROUND
The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology.
MATERIALS AND METHODS
We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data.
RESULTS
A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data.
CONCLUSION
AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.
Topics: Humans; Artificial Intelligence; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Medical Oncology
PubMed: 37879443
DOI: 10.1016/j.annonc.2023.10.125 -
European Neuropsychopharmacology : the... Nov 2023Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a... (Meta-Analysis)
Meta-Analysis Review
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.
Topics: Adult; Humans; Depression; Psilocybin; Antidepressive Agents; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37557019
DOI: 10.1016/j.euroneuro.2023.07.011 -
Frontiers in Neurology 2023Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all...
BACKGROUND
Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all available strategies targeting vasospasm and cerebral ischemia on outcomes in a network meta-analysis.
METHODS
We searched EMBASE and MEDLINE databases from 1 January 1990 and 28 November 2021 according to PRISMA guidelines. Randomized controlled trials and longitudinal studies were included. All curative or preventive strategies targeting vasospasm and/or cerebral ischemia were eligible. A network meta-analysis was performed to compare all interventions with one another in a primary (randomized controlled trials only) and a secondary analysis (both trials and longitudinal studies). Mortality by 3 months was the primary outcome. Secondary outcomes were vasospasm, neurological outcome by 3 months, and dichotomized as "good" or "poor" recovery according to each study definition.
RESULTS
A total of 2,382 studies were screened which resulted in the selection of 192 clinical trials (92 (47.9%) and 100 cohorts (52.1%) and the inclusion of 41,299 patients. In randomized controlled studies, no strategy decreased mortality by 3 months. Statins (0.79 [0.62-1]), tirilazad (0.82 [0.69-0.97]), CSF drainage (0.47 [0.29-0.77]), and clazosentan (0.51 [0.36-0.71]) significantly decreased the incidence of vasospasm. Cilostazol was the only treatment associated with improved neurological outcomes by 3 months in the primary (OR 1.16, 95% CI [1.05-1.28]) and secondary analyses (OR 2.97, 95% CI [1.39-6.32]).
DISCUSSION
In the modern era of subarachnoid hemorrhage, all strategies targeting vasospasm failed to decrease mortality. Cilostazol should be confirmed as a treatment to improve neurological outcomes. The link between vasospasm and neurological outcome appears questionable.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=116073, identifier: PROSPERO CRD42018116073.
PubMed: 37662039
DOI: 10.3389/fneur.2023.1217719 -
Sports Health 2023To determine optimal treatment strategies for shoulder impingement syndrome (SIS). (Meta-Analysis)
Meta-Analysis Review
CONTEXT
To determine optimal treatment strategies for shoulder impingement syndrome (SIS).
OBJECTIVE
To compare subacromial nonsteroidal anti-inflammatory injections (SNIs) and subacromial corticosteroid injections (SCIs) on pain relief and functional improvement in individuals with SIS. Second, to perform a cost analysis of the 2 injections.
DATA SOURCES
MEDLINE, SPORTDiscus, CINAHL, Embase, Web of Science, and SCOPUS databases were searched for randomized controlled trials using several keywords.
STUDY SELECTION
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized, and 10 studies comparing changes in pain or function in humans with SIS receiving SNIs or SCIs were included. Quality and risk of bias were assessed using the Consolidated Standards of Reporting Trials (CONSORT) 2010 scale and the Cochrane Collaboration tool.
STUDY DESIGN
Systematic review and meta-analysis.
LEVEL OF EVIDENCE
Level 1.
DATA EXTRACTION
Baseline and follow-up scores of the visual analog, Constant-Murley, and University of California Los Angeles shoulder scales were extracted to calculate effect sizes (ESs), represented as Cohen . Metaregression and publication bias analyses were performed. Procedural and medication costs were extracted from Medicare guidelines.
RESULTS
A total of 7 high and 3 good quality studies were included, with a mean score of 21.1. Only 1 study had a high risk of bias. The meta-analyses produced pooled ESs of 0.05 ( = 0.83), 0.12 ( = 0.71), and 0.07 ( = 0.79) for each scale, respectively, with CIs crossing 0. Procedural costs were equal between groups, whereas ketorolac was the least costly medication ($0.47). There was no significant difference in side effects between the 2 injections.
CONCLUSION
SNIs are as effective as SCIs for short-term pain relief and improving function in patients with subacromial impingement syndrome. In addition, they are less expensive and cause no major difference in complications, providing a viable, cost-effective alternative for injection therapy in patients with SIS.
Topics: Aged; United States; Humans; Shoulder Impingement Syndrome; Injections, Intra-Articular; Medicare; Anti-Inflammatory Agents, Non-Steroidal; Adrenal Cortex Hormones; Pain
PubMed: 35897160
DOI: 10.1177/19417381221108726 -
BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
Intensive Care Medicine Feb 2024Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a... (Meta-Analysis)
Meta-Analysis
PURPOSE
Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit.
METHODS
We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model.
RESULTS
We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66).
CONCLUSION
In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.
Topics: Humans; Shock, Cardiogenic; Propensity Score; Network Meta-Analysis; Randomized Controlled Trials as Topic; Heart-Assist Devices
PubMed: 38206381
DOI: 10.1007/s00134-023-07278-3 -
Family Process Sep 2023Single-parent families led by fathers are an increasing demographic globally, Furthermore, single fatherhood is associated with poorer self-reported health and mental...
Single-parent families led by fathers are an increasing demographic globally, Furthermore, single fatherhood is associated with poorer self-reported health and mental health, lifestyle practices and habits, increased health complications, psychological symptoms, hospital admissions, and higher mortality. However, there is still a dearth of evidence exploring single fathers' experiences. A systematic review and meta-synthesis were conducted using Sandelowski and Barroso's approach. Six electronic databases were searched from each database's inception to December 2021, and 34 studies were included in this review. In total, six themes were synthesized: (i) "Doing it alone": Double the work, stress, and tears; (ii) Beyond ambivalence and towards stability, (iii) Walking into the lion's den; (iv) Education as a foundation for a better future; (v) "Single but not alone": Support systems; (vi) "Reconceptualising my predicament": Double the love and growth. Our findings suggest the need to: help fathers better navigate their relationships with their children and ex-partners, increased awareness and availability of parent-teaching and support programs, and reform guidelines and policies to enable greater participation and involvement of fathers in future judicial systems, and social and public assistance services.
Topics: Male; Child; Humans; Parenting; Fathers; Single-Parent Family; Mental Health; Life Style
PubMed: 36305198
DOI: 10.1111/famp.12830 -
Resuscitation Dec 2023Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence... (Meta-Analysis)
Meta-Analysis Review
Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.
BACKGROUND
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established.
METHODS
We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.
FINDINGS
We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes).
INTERPRETATION
The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
Topics: Adult; Humans; Female; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation; Prognosis; Odds Ratio; Extracorporeal Membrane Oxygenation; Retrospective Studies
PubMed: 37863420
DOI: 10.1016/j.resuscitation.2023.110004 -
BMC Public Health Nov 2023Due to low vaccination uptake and measles outbreaks across Europe, public health authorities have paid increasing attention to anthroposophic communities. Public media...
BACKGROUND
Due to low vaccination uptake and measles outbreaks across Europe, public health authorities have paid increasing attention to anthroposophic communities. Public media outlets have further described these communities as vaccine refusers or "anti-vaxxers". The aim of this review was to understand the scope of the problem and explore assumptions about vaccination beliefs in anthroposophic communities. For the purpose of this review, we define anthroposophic communities as people following some/certain views more or less loosely connected to the philosophies of anthroposophy. The systematic review addresses three research questions and (1) collates evidence documenting outbreaks linked to anthroposophic communities, (2) literature on vaccination coverage in anthroposophic communities, and (3) lastly describes literature that summarizes theories and factors influencing vaccine decision-making in anthroposophic communities.
METHODS
This is a systematic review using the following databases: Medline, Web of Science, Psycinfo, and CINAHL. Double-blinded article screening was conducted by two researchers. Data was summarized to address the research questions. For the qualitative research question the data was analysed using thematic analysis with the assistance of Nvivo12.0.
RESULTS
There were 12 articles documenting 18 measles outbreaks linked to anthroposophic communities between the years 2000 and 2012. Seven articles describe lower vaccination uptake in anthroposophic communities than in other communities, although one article describes that vaccination coverage in low-income communities with a migrant background was lower than in the anthroposophic community they studied. We found eight articles examining factors and theories influencing vaccine decision making in anthroposophic communities. The qualitative analysis revealed four common themes. Firstly, there was a very broad spectrum of vaccine beliefs among the anthroposophic communities. Secondly, there was a consistent narrative about problems or concerns with vaccines, including toxicity and lack of trust in the system. Thirdly, there was a strong notion of the importance of making individual and well-informed choices as opposed to simply following the masses. Lastly, making vaccine choices different from public health guidelines was highly stigmatized by those outside of the anthroposophic community but also those within the community.
CONCLUSION
Continuing to further knowledge of vaccine beliefs in anthroposophic communities is particularly important in view of increasing measles rates and potential sudden reliance on vaccines for emerging diseases. However, popular assumptions about vaccine beliefs in anthroposophic communities are challenged by the data presented in this systematic review.
Topics: Humans; Anthroposophy; Vaccination Hesitancy; Vaccines; Vaccination; Measles
PubMed: 37957574
DOI: 10.1186/s12889-023-17081-w