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Archives of Dermatological Research Feb 2024Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a... (Meta-Analysis)
Meta-Analysis Review
Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a dysregulated immune response with a shift in the balance of neutrophils, lymphocytes and platelets. We sought to evaluate the novel systemic inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as psoriatic indicators. Pubmed, Web of Science and Scopus were systematically searched for relevant studies. Twenty-four studies consisting of a total of 2,275 psoriatic patients (1,301 males and 974 females) and 2,334 healthy controls (1,401 males and 933 females) were identified for inclusion in the quantitative analysis. The NLR and PLR were found to be significantly increased in psoriatic patients [standardized mean difference (SMD) = 0.68, 95% CI 0.56-0.80, p < 0.01, and SMD = 0.37, 95% CI 0.14-0.60, p < 0.01, respectively]. However, no association between the NLR and PLR with psoriasis severity was detected (p = 0.93, and p = 0.83, respectively). In conclusion, the NLR and PLR are simple and cost-effective markers of psoriatic presence, but their value as severity markers requires further study.
Topics: Humans; Female; Male; Neutrophils; Psoriasis; Skin; Lymphocytes
PubMed: 38329632
DOI: 10.1007/s00403-024-02823-6 -
The Journal of Antimicrobial... Jul 2023The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear.
METHODS
We conducted a systematic review until 1 November 2022 searching for randomized controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir [±standard of care (SoC)] versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach.
RESULTS
Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality [risk ratio (RR) 0.27, 95% CI 0.07-1.02, high-certainty evidence] and probably does not reduce the risk for 'hospitalization or death' (RR 0.81, 95% CI 0.55-1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02-1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92-1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50-28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence).
CONCLUSIONS
In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on 'hospitalization or death' and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.
Topics: Humans; COVID-19; SARS-CoV-2
PubMed: 37170886
DOI: 10.1093/jac/dkad132 -
The Lancet. Global Health Jun 2023Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests.
METHODS
In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337.
FINDINGS
We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies.
INTERPRETATION
AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples.
FUNDING
FIND, the Global Alliance for Diagnostics.
Topics: Humans; Male; Female; Sputum; Bayes Theorem; Cross-Sectional Studies; Tuberculosis; Lipopolysaccharides; HIV Infections; Sensitivity and Specificity; Mycobacterium tuberculosis
PubMed: 37202025
DOI: 10.1016/S2214-109X(23)00135-3 -
Neurology(R) Neuroimmunology &... May 2024Susac syndrome (SuS) is an orphan microangiopathic disease characterized by a triad of encephalopathy, visual disturbances due to branch retinal artery occlusions, and... (Review)
Review
Susac syndrome (SuS) is an orphan microangiopathic disease characterized by a triad of encephalopathy, visual disturbances due to branch retinal artery occlusions, and sensorineuronal hearing loss. Our previous systematic review on all cases of SuS reported until 2012 allowed for a better understanding of clinical presentation and diagnostic findings. Based on these data, we suggested diagnostic criteria in 2016 to allow early diagnosis and treatment of SuS. In view of the accumulation of new SuS cases reported in the last 10 years and improved diagnostic tools, we here aimed at updating the demographic and clinical features of SuS and to review the updated ancillary tests being used for SuS diagnosis. Therefore, based on the 2016 criteria, we systematically collected and evaluated data on SuS published from January 2013 to March 2022.
Topics: Humans; Susac Syndrome; Magnetic Resonance Imaging; Brain Diseases; Vision Disorders; Diagnosis, Differential
PubMed: 38364193
DOI: 10.1212/NXI.0000000000200209 -
Cancer Management and Research 2022Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs). (Review)
Review
BACKGROUND
Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs).
METHODS
We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs.
RESULTS
A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%).
CONCLUSION
This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin.
PubMed: 36575665
DOI: 10.2147/CMAR.S372776 -
Nature Communications Sep 2023COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be... (Meta-Analysis)
Meta-Analysis
COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.
Topics: Humans; COVID-19; Proteome; Proteomics; SARS-CoV-2; Cytoplasm
PubMed: 37739942
DOI: 10.1038/s41467-023-41159-z -
Indian Journal of Gastroenterology :... Oct 2021Celiac disease (CD) primarily affects the small intestine. Previous studies have identified higher incidences of neuropsychiatric diseases among CD patients compared to... (Meta-Analysis)
Meta-Analysis Review
Celiac disease (CD) primarily affects the small intestine. Previous studies have identified higher incidences of neuropsychiatric diseases among CD patients compared to non-CD controls. Genome-wide association studies have identified >60 non-human leukocyte antigen (HLA) genes associated with CD, where estimated 15% genes have role in neurological health. We carried out a systematic review and meta-analysis to estimate the potential risk conferred by CD in developing neuropsychiatric diseases. Literature search was performed till June 2019. Incidences of neuropsychiatric diseases were compared among CD and non-CD controls. Funnel plots and Egger's tests were used to evaluate publication bias and estimate study effects. Qualities of the included studies were estimated using Newcastle-Ottawa Scale. Quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Odds of developing neuropsychiatric diseases among CD were evaluated by computing meta-odds ratio (Manten-Haenszel method) and Z test p-value using random and fixed effect models based on the degree of study heterogeneity. Thirteen non-randomized case-control studies were found eligible. Subjects suffering from CD were found to have significantly more risk to develop depression (p<1.00E-05; OR=1.60 [1.37-1.86]), anxiety (p=0.05; OR=1.41 [1.00-1.97]), headache (p<0.1.00E-05; OR=3.27 [2.46-4.34]), epilepsy (p<1.00E-04; OR=11.90 [3.78-37.43]), panic disorder (p<1.00E-04; OR=4.64 [2.22-9.70]), and dysthymia (p=2.00E-03; OR=5.27 [1.83-15.22]). CD is a major predisposing factor in developing array of common neuropsychiatric diseases. Shared biological processes and molecular networks could play a crucial role in disease co-occurrence. Detailed molecular evidences are needed to establish the cause-effect relationship between these diseases.
Topics: Anxiety; Celiac Disease; Depression; Dysthymic Disorder; Epilepsy; Genome-Wide Association Study; Headache; Humans; Panic Disorder
PubMed: 34839445
DOI: 10.1007/s12664-021-01215-2 -
Parasites & Vectors Jan 2022Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral... (Meta-Analysis)
Meta-Analysis Review
Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). Addressing the need for a PoC test, several diagnostic tests, including serological and molecular methods, have been developed and evaluated in the past. One promising molecular method, already implemented for diagnosis of a range of diseases, is the loop-mediated isothermal amplification (LAMP) protocol. In this systematic review and meta-analysis, using a comprehensive search strategy, we focus on studies evaluating the performance of LAMP for the diagnosis of leishmaniasis in humans and other mammals such as dogs, compared with microscopy and/or any other molecular diagnostic method. A meta-analysis, pooling sensitivity and specificity rates and calculating areas under the curve (AUCs) in summary receiver operating characteristic (SROC) plots, was conducted on datasets extracted from studies, grouped by clinical condition and sample type. We found high sensitivity and specificity for LAMP when compared with microscopy and PCR using blood samples, with pooled estimate values of > 90% for all subgroups, corresponding to calculated AUC values > 0.96, except for LAMP compared to microscopy for diagnosis of CL. However, only a limited number of studies were truly comparable. Most of the observed heterogeneity is likely based on true differences between the studies rather than sampling error only. Due to simple readout methods and low laboratory equipment requirements for sample preparation compared to other molecular methods, LAMP is a promising candidate for a molecular (near-)PoC diagnostic method for VL and CL.
Topics: Animals; Dogs; Genes, Protozoan; Humans; Leishmania; Leishmaniasis, Visceral; Molecular Diagnostic Techniques; Neglected Diseases; Nucleic Acid Amplification Techniques; Pathology, Molecular
PubMed: 35073980
DOI: 10.1186/s13071-021-05133-2 -
Molecular Therapy. Nucleic Acids Mar 2022Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent... (Review)
Review
Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent evidence suggests miR-221 as a fine-tuner of chronic liver injury and inflammation-related events. Available information also supports the potential of miR-221 silencing as promising therapeutic intervention. In this systematic review, we selected papers from the principal databases (PubMed, MedLine, Medscape, ASCO, ESMO) between January 2012 and December 2020, using the keywords "miR-221" and the specific keywords related to the most important hematologic and solid malignancies, and some non-malignant diseases, to define and characterize deregulated miR-221 as a valuable therapeutic target in the modern vision of molecular medicine. We found a major role of miR-221 in this view.
PubMed: 35282417
DOI: 10.1016/j.omtn.2022.02.005 -
Translational Psychiatry Jun 2023The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the... (Meta-Analysis)
Meta-Analysis
The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.
Topics: Adolescent; Child; Humans; Molecular Epidemiology; Twins, Dizygotic; Databases, Factual; Research Design
PubMed: 37380645
DOI: 10.1038/s41398-023-02433-2