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Diagnostic Pathology Apr 2022The early detection of coronavirus disease (COVID-19) infection to improve disease management becomes the greatest challenge. Despite the high sensitivity of RT-PCR, not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The early detection of coronavirus disease (COVID-19) infection to improve disease management becomes the greatest challenge. Despite the high sensitivity of RT-PCR, not only it was reported that 20-67% of infected patients had false-negative results. Rapid diagnostic tests (RDTs) are widely used as a point-of-care test for SARS-CoV-2 detection in pharyngeal and blood specimens. It's more appealing since it's less time-consuming, doesn't seem to be as expensive, and doesn't need any specific training, but the poor sensitivity is the major limitation. Several reports indicated the rapid test of blood and pharyngeal samples has the same sensitivity as the RT-PCR, but some reports have lower sensitivity, especially in asymptomatic patients.
METHODS
In the present survey, we investigate the eligible studies for the sensitivity and specificity of rapid tests and explore the factors that influence the result to help better diagnose COVID-19 infection. 20 studies met the inclusion criteria which imposed 33 different tests.
RESULTS
Our findings showed the type of sample, the type of assay, the time of sampling, and the load of virus influence on the sensitivity of RDTs.
CONCLUSION
This research extends our knowledge of how to improve the sensitivity of RDTs to better diagnose the infected patients to address the controlling COVID-19 pandemic.
Topics: COVID-19; Diagnostic Tests, Routine; Humans; Pandemics; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35414002
DOI: 10.1186/s13000-022-01215-6 -
Nature Communications Mar 2022Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but... (Meta-Analysis)
Meta-Analysis
Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but lack of centralized databases is hampering an overall outcomes assessment. Here we aim to provide a comprehensive assessment of the short and long term safety of HSPC-GT from trials using different vector platforms. We review systematically the literature on HSPC-GT to describe survival, genotoxicity and engraftment of gene corrected cells. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death is 0.9 per 100 person-years of observation (PYO) (95% CI = 0.37-2.17). There are 21 genotoxic events out of 1504.02 PYO, which occurred in γRV trials (0.99 events per 100 PYO, 95% CI = 0.18-5.43) for primary immunodeficiencies. Pooled rate of engraftment is 86.7% (95% CI = 67.1-95.5%) for γRV and 98.7% (95% CI = 94.5-99.7%) for LV HSPC-GT (p = 0.005). Our analyses show stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPCs.
Topics: Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lentivirus
PubMed: 35288539
DOI: 10.1038/s41467-022-28762-2 -
Annals of Medicine Dec 2022Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the...
INTRODUCTION
Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients.
METHODS
This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943.
RESULTS
Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature ( = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection.
CONCLUSION
EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.KEY MESSAGESExtramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before.There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities.More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.
Topics: Adult; Blood Transfusion; Hematopoiesis, Extramedullary; Humans; Magnetic Resonance Imaging; Retrospective Studies; beta-Thalassemia
PubMed: 35261317
DOI: 10.1080/07853890.2022.2048065 -
Frontiers in Psychiatry 2021This systematic review and meta-analysis aimed to evaluate the effectiveness of virtual reality (VR)-based technology on emotional response and symptoms in patients with...
This systematic review and meta-analysis aimed to evaluate the effectiveness of virtual reality (VR)-based technology on emotional response and symptoms in patients with obsessive-compulsive disorder (OCD). We systematically searched major electronic databases, including PubMed/Medline, Scopus, Embase, ISI Web of Science, PsycINFO, and Cochrane central, up to April 14, 2021, with no data or language limits. We performed reference, related articles, and citation searches to find additional articles. We included original articles comparing and studying VR-based technology in patients with OCD against the control group. We observed that VR significantly increases in anxiety (SMD = 2.92; 95% CI 1.89-3.94, < 0.0001; = 95%), disgust (SMD = 2.52; 95% CI 1.36-3.68, < 0.0001; = 95%), urge to wash (SMD = 3.12; 95% CI 1.92-4.32, < 0.0001; = 94%), checking time (SMD = 1.06; 95% CI 0.71-1.4, < 0.0001; = 44%), number of checking behavior (SMD = 1.45; 95% CI 0.06-2.83, = 0.04; = 93%), and uncertainty (SMD = 2.59; 95% CI 0.90-4.27, = 0.003; = 70%) in OCD patients compared with healthy controls using a random-effect model. This meta-analysis found that this environment has a moderate enhancement in emotional response and symptoms test scores of patients with OCD. However, our findings should be generalized with caution due to the lack of standardized methods and high heterogeneity among included evidence. The appropriate mode of integrating VR-based technology for patients with OCD requires more exploration.
PubMed: 35177996
DOI: 10.3389/fpsyt.2021.733584 -
Annals of Medicine Dec 2022Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no...
INTRODUCTION
Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents.
METHODS
This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria.
RESULTS
Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report ( = 15/36, 41.7%), and pill count ( = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills ( = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence ( = 29) or "quantitatively" as a percentage of medication taken out of those prescribed ( = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis.
CONCLUSIONS
Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.
Topics: Adolescent; Chelation Therapy; Child; Humans; Iron; Iron Overload; Patient Compliance; Thalassemia
PubMed: 35103514
DOI: 10.1080/07853890.2022.2028894 -
Value in Health : the Journal of the... Feb 2022Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies...
OBJECTIVES
Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation.
METHODS
Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values.
RESULTS
Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers.
CONCLUSIONS
There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.
Topics: Adult; Anemia, Sickle Cell; Antisickling Agents; Blood Transfusion; Child; Comorbidity; Cost-Benefit Analysis; Female; Health Status Indicators; Humans; Hydroxyurea; Male; Outcome Assessment, Health Care; Pain; Quality of Life; Quality-Adjusted Life Years; Surveys and Questionnaires
PubMed: 35094801
DOI: 10.1016/j.jval.2021.08.002 -
Haematologica Aug 2022Whether corticosteroids improve outcome in patients with acute complications of sickle cell disease (SCD) is still debated. We performed a systematic review of the... (Meta-Analysis)
Meta-Analysis
Whether corticosteroids improve outcome in patients with acute complications of sickle cell disease (SCD) is still debated. We performed a systematic review of the literature with the aim of estimating effects of corticosteroids on the clinical course of vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) in patients with SCD. The primary outcome was transfusion requirement during hospitalization. Studies were identified by search of MEDLINE and CENTRAL database. Three randomized clinical trials (RCT) and three retrospective cohort studies (RCS) were included, involving 3,304 participants and 5,562 VOC or ACS episodes. There was no difference between corticosteroids and standard treatment regarding transfusion requirement overall (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.38-2.53) but there was a significant interaction of the study type (P<0.0001): corticosteroid therapy was associated with a lower risk of transfusion in RCT (OR=0.13, 95% CI: 0.04-0.45) and a higher risk of transfusion in RCS (OR=2.12, 95% CI: 1.33-3.40. In RCT, the length of hospital stay was lower with corticosteroids as compared with standard treatment: mean difference - 24 hours (95% CI: -35 to -14). Corticosteroids were associated with an increased risk of hospital readmission as compared with standard treatment, in RCT, RCS, and the entire cohort: OR=5.91, 95% CI: 1.40-24.83; OR=3.28, 95% CI: 1.46-7.36 and OR=3.21, 95% CI: 1.97-5.24, respectively. Corticosteroids were associated with reduced number of transfusions and length of stay in RCT but not in RCS, with more rehospitalizations overall. Additional RCT should be conducted while minimizing the risk of rehospitalizations.
Topics: Adrenal Cortex Hormones; Anemia, Sickle Cell; Blood Transfusion; Humans; Volatile Organic Compounds
PubMed: 35021607
DOI: 10.3324/haematol.2021.280105 -
Iranian Journal of Medical Sciences Jan 2022Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of depression among patients with BT in Iran.
METHODS
Domestic and international databases were searched for relevant articles published from 1991 until June 2019. We searched international databases such as Scopus, ISI, and Embase; Iranian databases such as SID, Magiran, and IranDoc; and Google Scholar and PubMed search engines. The MeSH keywords used were "depression", "mental health", "depressive disorder", "thalassemia", "beta-thalassemia major", "prevalence", "epidemiology", and "Iran". Relevant cross-sectional or cohort studies were included in the analysis. Cochran's test and the index were used to assess heterogeneity. The pooled prevalence and its 95% confidence interval (CI) were calculated using "metaprop" commands in Stata 14. In cases, where the statistic was greater than 50%, the random-effects model was used.
RESULTS
Eighteen eligible studies were included. The pooled prevalence of depression was 42% (95% CI: 33% to 52%), whereas the pooled prevalence of mild, moderate, severe, and extremely severe depression was 16% (95% CI: 11% to 22%), 13% (95% CI: 9% to 18%), 13% (95% CI: 9% to 17%), and 3% (95% CI: 0% to 8%), respectively. The pooled prevalence of depression in moderate- and high-quality studies was 45% (95% CI: 29% to 61%), and 39% (95% CI: 27% to 51%), respectively.
CONCLUSION
The high prevalence of depression highlights the urgent need for the establishment of interventions for the prevention, early detection, and treatment of depression among Iranian patients with BT.
Topics: Cross-Sectional Studies; Depression; Humans; Iran; Prevalence; beta-Thalassemia
PubMed: 35017773
DOI: 10.30476/ijms.2020.85941.1557 -
Journal of Clinical Medicine Dec 2021In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments.... (Review)
Review
In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments. The improved survival, however, has allowed for the emergence of comorbidities, such as hearing loss, with a non-negligible impact on the patients' quality of life. This thorough review analyzes the acquired knowledge regarding hearing impairment in this hereditary hemoglobinopathy, aiming at defining its prevalence, features, course, and possible disease- or treatment-related pathogenic factors. Following PRISMA criteria, we retrieved 60 studies published between 1979 and 2021. Diagnostic tools and criteria, forms of hearing impairment, correlations with beta-thalassemia phenotypes, age and sex, chelation treatment and laboratory findings including iron overload, were carefully searched, analyzed and summarized. In spite of the relatively high number of studies in the last 40 years, our knowledge is rather limited, and large prospective studies with homogeneous diagnostic tools and criteria are required to define all the aforementioned issues. According to the literature, the overall prevalence rate of hearing impairment is 32.3%; age, sex, and laboratory findings do not seem to correlate with hearing deficits, while the weak relationship with clinical phenotype and chelation treatment seems to highlight the presence of further yet to be identified pathogenic factors.
PubMed: 35011846
DOI: 10.3390/jcm11010102 -
The Cochrane Database of Systematic... Dec 2021Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of... (Review)
Review
BACKGROUND
Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015.
OBJECTIVES
To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS
The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS
Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS
Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certainty of the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, we judged the certainty of the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certainty of this evidence to be very low.
Topics: Albuminuria; Anemia, Sickle Cell; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Humans; Proteinuria; Randomized Controlled Trials as Topic
PubMed: 34932828
DOI: 10.1002/14651858.CD009191.pub4