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Journal of Medical Virology Jan 2023The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or... (Review)
Review
The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome. A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.
Topics: Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Multiple Organ Failure
PubMed: 36349400
DOI: 10.1002/jmv.28289 -
International Journal of Infectious... Mar 2020To provide better management of Fournier's gangrene, mortality-associated comorbidities and common etiologies were identified. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To provide better management of Fournier's gangrene, mortality-associated comorbidities and common etiologies were identified.
METHODS
A systematic search was conducted using 12 databases, followed by meticulous screening to select relevant articles. Meta-analysis and meta-regression (for possible cofounders) were both done for all possible outcomes.
RESULTS
Out of 1186 reports screened, 38 studies were finally included in the systematic review and meta-analysis. A higher risk of mortality was detected in patients with diabetes, heart disease, renal failure, and kidney disease, with risk ratios (RR) and 95% confidence intervals (95% CI) of 0.72 (0.59-0.89), 0.39 (0.24-0.62), 0.41 (0.27-0.63), and 0.34 (95% CI 0.16-0.73), respectively. However, there was no association between mortality rates and comorbid hypertension, lung disease, liver disease, or malignant disease (p > 0.05). The highest mortality rates were due to sepsis (76%) and multiple organ failure (66%), followed by respiratory (19.4%), renal (18%), cardiovascular (15.7%), and hepatic (5%) mortality.
CONCLUSIONS
Modifications to the Fournier's Gangrene Severity Index (FGSI) are recommended, in order to include comorbidities as an important prognostic tool for FG mortality. Close monitoring of the patients, with special interest given to the main causes of mortality, is an essential element of the management process.
Topics: Cause of Death; Comorbidity; Fournier Gangrene; Humans; Prognosis; Retrospective Studies; Sepsis; Severity of Illness Index; Survival Rate
PubMed: 31962181
DOI: 10.1016/j.ijid.2019.12.030 -
Annals of Palliative Medicine Oct 2021Nutritional support is very important in the treatment of severe acute pancreatitis, this study aimed to investigate the effect of total parenteral nutrition (TPN) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nutritional support is very important in the treatment of severe acute pancreatitis, this study aimed to investigate the effect of total parenteral nutrition (TPN) and enteral nutrition (TEN) on the prognosis of patients with acute pancreatitis.
METHODS
The databases of PubMed, Embase, Cochrane Library, and Ovid were searched using the keywords acute pancreatitis, enteral nutrition, and parenteral nutrition to obtain the reports of randomized controlled trials (RCTs) published after 2000. After screening the articles according to the inclusion criteria, risk of bias of the included literatures was evaluated using the Cochrane Handbook for Systematic Reviews. The software RevMan 5.3.5 was used for analysis and the creation of a forest plot and funnel plot.
RESULTS
A total of 488 literatures were preliminarily searched in this study, from which 10 articles were included into the final quantitative analysis, involving a total of 699 participants. A total of 6 literatures (n=329 participants) reported the infection rate indicators. The obtained statistic value [odds ratio (OR) =0.25, 95% confidence interval (CI): 0.10 to 0.62] showed TEN had less infection rate that TPN (P=0.003). A total of 8 studies (654 participants) reported the incidence rate indicators of multiple organ failure rate indicator, the obtained statistic value (OR =0.50, 95% CI: 0.24 to 1.08) showed no statistical difference between TEN and TPN (P>0.05). A total of 7 studies (550 participants) reported the mortality indicators. The obtained statistic value (OR =0.59, 95% CI: 0.37 to 0.94) showed TEN had less mortality than TPN (P=0.03). A total of 3 studies reported the length of hospital stay indicators. The obtained statistic value [mean difference (MD) -4.18, 95% CI: -5.07 to -3.30] showed the length of hospital stay for TEN was shorter that TPN (P<0.001).
DISCUSSION
Compared with TPN, TEN can reduce the incidence of infection, reduce the development of multiple organ failure, reduce mortality, and shorten the length of hospital stay in patients with severe acute pancreatitis (SAP). However, attention should be paid to prevent the occurrence of complications during the implementation of nutritional intervention.
Topics: Enteral Nutrition; Humans; Pancreatitis; Parenteral Nutrition; Parenteral Nutrition, Total; Prognosis
PubMed: 34763439
DOI: 10.21037/apm-21-2469 -
The Cochrane Database of Systematic... Feb 2022Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria since it was first introduced in Malawi in 1993 (Filler 2006). Due to increasing resistance to SP, in 2000 the WHO recommended that one of several artemisinin-based combination therapies (ACTs) be used instead of SP for the treatment of uncomplicated malaria caused by Plasmodium falciparum (Global Partnership to Roll Back Malaria 2001). However, despite these recommendations, SP continues to be advised for intermittent preventive treatment in pregnancy (IPTp) and intermittent preventive treatment in infants (IPTi), whether the person has malaria or not (WHO 2013). Description of the intervention Folate (vitamin B9) includes both naturally occurring folates and folic acid, the fully oxidized monoglutamic form of the vitamin, used in dietary supplements and fortified food. Folate deficiency (e.g. red blood cell (RBC) folate concentrations of less than 305 nanomoles per litre (nmol/L); serum or plasma concentrations of less than 7 nmol/L) is common in many parts of the world and often presents as megaloblastic anaemia, resulting from inadequate intake, increased requirements, reduced absorption, or abnormal metabolism of folate (Bailey 2015; WHO 2015a). Pregnant women have greater folate requirements; inadequate folate intake (evidenced by RBC folate concentrations of less than 400 nanograms per millilitre (ng/mL), or 906 nmol/L) prior to and during the first month of pregnancy increases the risk of neural tube defects, preterm delivery, low birthweight, and fetal growth restriction (Bourassa 2019). The WHO recommends that all women who are trying to conceive consume 400 micrograms (µg) of folic acid daily from the time they begin trying to conceive through to 12 weeks of gestation (WHO 2017). In 2015, the WHO added the dosage of 0.4 mg of folic acid to the essential drug list (WHO 2015c). Alongside daily oral iron (30 mg to 60 mg elemental iron), folic acid supplementation is recommended for pregnant women to prevent neural tube defects, maternal anaemia, puerperal sepsis, low birthweight, and preterm birth in settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin (Hb) concentration of less than 110 g/L). How the intervention might work Potential interactions between folate status and malaria infection The malaria parasite requires folate for survival and growth; this has led to the hypothesis that folate status may influence malaria risk and severity. In rhesus monkeys, folate deficiency has been found to be protective against Plasmodium cynomolgi malaria infection, compared to folate-replete animals (Metz 2007). Alternatively, malaria may induce or exacerbate folate deficiency due to increased folate utilization from haemolysis and fever. Further, folate status measured via RBC folate is not an appropriate biomarker of folate status in malaria-infected individuals since RBC folate values in these individuals are indicative of both the person's stores and the parasite's folate synthesis. A study in Nigeria found that children with malaria infection had significantly higher RBC folate concentrations compared to children without malaria infection, but plasma folate levels were similar (Bradley-Moore 1985). Why it is important to do this review The malaria parasite needs folate for survival and growth in humans. For individuals, adequate folate levels are critical for health and well-being, and for the prevention of anaemia and neural tube defects. Many countries rely on folic acid supplementation to ensure adequate folate status in at-risk populations. Different formulations for folic acid supplements are available in many international settings, with dosages ranging from 400 µg to 5 mg. Evaluating folic acid dosage levels used in supplementation efforts may increase public health understanding of its potential impacts on malaria risk and severity and on treatment failures. Examining folic acid interactions with antifolate antimalarial medications and with malaria disease progression may help countries in malaria-endemic areas determine what are the most appropriate lower dose folic acid formulations for at-risk populations. The WHO has highlighted the limited evidence available and has indicated the need for further research on biomarkers of folate status, particularly interactions between RBC folate concentrations and tuberculosis, human immunodeficiency virus (HIV), and antifolate antimalarial drugs (WHO 2015b). An earlier Cochrane Review assessed the effects and safety of iron supplementation, with or without folic acid, in children living in hyperendemic or holoendemic malaria areas; it demonstrated that iron supplementation did not increase the risk of malaria, as indicated by fever and the presence of parasites in the blood (Neuberger 2016). Further, this review stated that folic acid may interfere with the efficacy of SP; however, the efficacy and safety of folic acid supplementation on these outcomes has not been established. This review will provide evidence on the effectiveness of daily folic acid supplementation in healthy and malaria-infected individuals living in malaria-endemic areas. Additionally, it will contribute to achieving both the WHO Global Technical Strategy for Malaria 2016-2030 (WHO 2015d), and United Nations Sustainable Development Goal 3 (to ensure healthy lives and to promote well-being for all of all ages) (United Nations 2021), and evaluating whether the potential effects of folic acid supplementation, at different doses (e.g. 0.4 mg, 1 mg, 5 mg daily), interferes with the effect of drugs used for prevention or treatment of malaria.
OBJECTIVES
To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?
METHODS
Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (including but not limited to sulfadoxine/pyrimethamine (SP), pyrimethamine-dapsone, pyrimethamine, chloroquine and proguanil, cotrimoxazole) for the prevention or treatment of malaria (studies will be included if more than 70% of the participants live in malaria-endemic regions) Studies assessing participants with or without anaemia and with or without malaria parasitaemia at baseline will be included Exclusion criteria Individuals not taking antifolate antimalarial medications for prevention or treatment of malaria Individuals living in non-malaria endemic areas Types of interventions Inclusion criteria Folic acid supplementation Form: in tablet, capsule, dispersible tablet at any dose, during administration, or periodically Timing: during, before, or after (within a period of four to six weeks) administration of antifolate antimalarials Iron-folic acid supplementation Folic acid supplementation in combination with co-interventions that are identical between the intervention and control groups. Co-interventions include: anthelminthic treatment; multivitamin or multiple micronutrient supplementation; 5-methyltetrahydrofolate supplementation. Exclusion criteria Folate through folate-fortified water Folic acid administered through large-scale fortification of rice, wheat, or maize Comparators Placebo No treatment No folic acid/different doses of folic acid Iron Types of outcome measures Primary outcomes Uncomplicated malaria (defined as a history of fever with parasitological confirmation; acceptable parasitological confirmation will include rapid diagnostic tests (RDTs), malaria smears, or nucleic acid detection (i.e. polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), etc.)) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Severe malaria (defined as any case with cerebral malaria or acute P. falciparum malaria, with signs of severity or evidence of vital organ dysfunction, or both) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Parasite clearance (any Plasmodium species), defined as the time it takes for a patient who tests positive at enrolment and is treated to become smear-negative or PCR negative. This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Treatment failure (defined as the inability to clear malaria parasitaemia or prevent recrudescence after administration of antimalarial medicine, regardless of whether clinical symptoms are resolved) (WHO 2019). This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Secondary outcomes Duration of parasitaemia Parasite density Haemoglobin (Hb) concentrations (g/L) Anaemia: severe anaemia (defined as Hb less than 70 g/L in pregnant women and children aged six to 59 months; and Hb less than 80 g/L in other populations); moderate anaemia (defined as Hb less than 100 g/L in pregnant women and children aged six to 59 months; and less than 110 g/L in others) Death from any cause Among pregnant women: stillbirth (at less than 28 weeks gestation); low birthweight (less than 2500 g); active placental malaria (defined as Plasmodium detected in placental blood by smear or PCR, or by Plasmodium detected on impression smear or placental histology). Search methods for identification of studies A search will be conducted to identify completed and ongoing studies, without date or language restrictions. Electronic searches A search strategy will be designed to include the appropriate subject headings and text word terms related to each intervention of interest and study design of interest (see Appendix 1). Searches will be broken down by these two criteria (intervention of interest and study design of interest) to allow for ease of prioritization, if necessary. The study design filters recommended by the Scottish Intercollegiate Guidelines Network (SIGN), and those designed by Cochrane for identifying clinical trials for MEDLINE and Embase, will be used (SIGN 2020). There will be no date or language restrictions. Non-English articles identified for inclusion will be translated into English. If translations are not possible, advice will be requested from the Cochrane Infectious Diseases Group and the record will be stored in the "Awaiting assessment" section of the review until a translation is available. The following electronic databases will be searched for primary studies. Cochrane Central Register of Controlled Trials. Cumulative Index to Nursing and Allied Health Literature (CINAHL). Embase. MEDLINE. Scopus. Web of Science (both the Social Science Citation Index and the Science Citation Index). We will conduct manual searches of ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the United Nations Children's Fund (UNICEF) Evaluation and Research Database (ERD), in order to identify relevant ongoing or planned trials, abstracts, and full-text reports of evaluations, studies, and surveys related to programmes on folic acid supplementation in malaria-endemic areas. Additionally, manual searches of grey literature to identify RCTs that have not yet been published but are potentially eligible for inclusion will be conducted in the following sources. Global Index Medicus (GIM). African Index Medicus (AIM). Index Medicus for the Eastern Mediterranean Region (IMEMR). Latin American & Caribbean Health Sciences Literature (LILACS). Pan American Health Organization (PAHO). Western Pacific Region Index Medicus (WPRO). Index Medicus for the South-East Asian Region (IMSEAR). The Spanish Bibliographic Index in Health Sciences (IBECS) (ibecs.isciii.es/). Indian Journal of Medical Research (IJMR) (journals.lww.com/ijmr/pages/default.aspx). Native Health Database (nativehealthdatabase.net/). Scielo (www.scielo.br/). Searching other resources Handsearches of the five journals with the highest number of included studies in the last 12 months will be conducted to capture any relevant articles that may not have been indexed in the databases at the time of the search. We will contact the authors of included studies and will check reference lists of included papers for the identification of additional records. For assistance in identifying ongoing or unpublished studies, we will contact the Division of Nutrition, Physical Activity, and Obesity (DNPAO) and the Division of Parasitic Diseases and Malaria (DPDM) of the CDC, the United Nations World Food Programme (WFP), Nutrition International (NI), Global Alliance for Improved Nutrition (GAIN), and Hellen Keller International (HKI). Data collection and analysis Selection of studies Two review authors will independently screen the titles and abstracts of articles retrieved by each search to assess eligibility, as determined by the inclusion and exclusion criteria. Studies deemed eligible for inclusion by both review authors in the abstract screening phase will advance to the full-text screening phase, and full-text copies of all eligible papers will be retrieved. If full articles cannot be obtained, we will attempt to contact the authors to obtain further details of the studies. If such information is not obtained, we will classify the study as "awaiting assessment" until further information is published or made available to us. The same two review authors will independently assess the eligibility of full-text articles for inclusion in the systematic review. If any discrepancies occur between the studies selected by the two review authors, a third review author will provide arbitration. Each trial will be scrutinized to identify multiple publications from the same data set, and the justification for excluded trials will be documented. A PRISMA flow diagram of the study selection process will be presented to provide information on the number of records identified in the literature searches, the number of studies included and excluded, and the reasons for exclusion (Moher 2009). The list of excluded studies, along with their reasons for exclusion at the full-text screening phase, will also be created. Data extraction and management Two review authors will independently extract data for the final list of included studies using a standardized data specification form. Discrepancies observed between the data extracted by the two authors will be resolved by involving a third review author and reaching a consensus. Information will be extracted on study design components, baseline participant characteristics, intervention characteristics, and outcomes. For individually randomized trials, we will record the number of participants experiencing the event and the number analyzed in each treatment group or the effect estimate reported (e.g. risk ratio (RR)) for dichotomous outcome measures. For count data, we will record the number of events and the number of person-months of follow-up in each group. If the number of person-months is not reported, the product of the duration of follow-up and the number of children evaluated will be used to estimate this figure. We will calculate the rate ratio and standard error (SE) for each study. Zero events will be replaced by 0.5. We will extract both adjusted and unadjusted covariate incidence rate ratios if they are reported in the original studies. For continuous data, we will extract means (arithmetic or geometric) and a measure of variance (standard deviation (SD), SE, or confidence interval (CI)), percentage or mean change from baseline, and the numbers analyzed in each group. SDs will be computed from SEs or 95% CIs, assuming a normal distribution of the values. Haemoglobin values in g/dL will be calculated by multiplying haematocrit or packed cell volume values by 0.34, and studies reporting haemoglobin values in g/dL will be converted to g/L. In cluster-randomized trials, we will record the unit of randomization (e.g. household, compound, sector, or village), the number of clusters in the trial, and the average cluster size. The statistical methods used to analyze the trials will be documented, along with details describing whether these methods adjusted for clustering or other covariates. We plan to extract estimates of the intra-cluster correlation coefficient (ICC) for each outcome. Where results are adjusted for clustering, we will extract the treatment effect estimate and the SD or CI. If the results are not adjusted for clustering, we will extract the data reported. Assessment of risk of bias in included studies Two review authors (KSC, LFY) will independently assess the risk of bias for each included trial using the Cochrane 'Risk of bias 2' tool (RoB 2) for randomized studies (Sterne 2019). Judgements about the risk of bias of included studies will be made according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). Disagreements will be resolved by discussion, or by involving a third review author. The interest of our review will be to assess the effect of assignment to the interventions at baseline. We will evaluate each primary outcome using the RoB2 tool. The five domains of the Cochrane RoB2 tool include the following. Bias arising from the randomization process. Bias due to deviations from intended interventions. Bias due to missing outcome data. Bias in measurement of the outcome. Bias in selection of the reported result. Each domain of the RoB2 tool comprises the following. A series of 'signalling' questions. A judgement about the risk of bias for the domain, facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement. Free-text boxes to justify responses to the signalling questions and 'Risk of bias' judgements. An option to predict (and explain) the likely direction of bias. Responses to signalling questions elicit information relevant to an assessment of the risk of bias. These response options are as follows. Yes (may indicate either low or high risk of bias, depending on the most natural way to ask the question). Probably yes. Probably no. No. No information (may indicate no evidence of that problem or an absence of information leading to concerns about there being a problem). Based on the answer to the signalling question, a 'Risk of bias' judgement is assigned to each domain. These judgements include one of the following. High risk of bias Low risk of bias Some concerns To generate the risk of bias judgement for each domain in the randomized studies, we will use the Excel template, available at www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2. This file will be stored on a scientific data website, available to readers. Risk of bias in cluster randomized controlled trials For the cluster randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 1b (bias arising from the timing of identification or recruitment of participants) and its related signalling questions. To generate the risk of bias judgement for each domain in the cluster RCTs, we will use the Excel template available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-cluster-randomized-trials. This file will be stored on a scientific data website, available to readers. Risk of bias in cross-over randomized controlled trials For cross-over randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 2 (bias due to deviations from intended interventions), and Domain 3 (bias due to missing outcome data), and their respective signalling questions. To generate the risk of bias judgement for each domain in the cross-over RCTs, we will use the Excel template, available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-crossover-trials, for each risk of bias judgement of cross-over randomized studies. This file will be stored on a scientific data website, available to readers. Overall risk of bias The overall 'Risk of bias' judgement for each specific trial being assessed will be based on each domain-level judgement. The overall judgements include the following. Low risk of bias (the trial is judged to be at low risk of bias for all domains). Some concerns (the trial is judged to raise some concerns in at least one domain but is not judged to be at high risk of bias for any domain). High risk of bias (the trial is judged to be at high risk of bias in at least one domain, or is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result). The 'risk of bias' assessments will inform our GRADE evaluations of the certainty of evidence for our primary outcomes presented in the 'Summary of findings' tables and will also be used to inform the sensitivity analyses; (see Sensitivity analysis). If there is insufficient information in study reports to enable an assessment of the risk of bias, studies will be classified as "awaiting assessment" until further information is published or made available to us. Measures of treatment effect Dichotomous data For dichotomous data, we will present proportions and, for two-group comparisons, results as average RR or odds ratio (OR) with 95% CIs. Ordered categorical data Continuous data We will report results for continuous outcomes as the mean difference (MD) with 95% CIs, if outcomes are measured in the same way between trials. Where some studies have reported endpoint data and others have reported change-from-baseline data (with errors), we will combine these in the meta-analysis, if the outcomes were reported using the same scale. We will use the standardized mean difference (SMD), with 95% CIs, to combine trials that measured the same outcome but used different methods. If we do not find three or more studies for a pooled analysis, we will summarize the results in a narrative form. Unit of analysis issues Cluster-randomized trials We plan to combine results from both cluster-randomized and individually randomized studies, providing there is little heterogeneity between the studies. If the authors of cluster-randomized trials conducted their analyses at a different level from that of allocation, and they have not appropriately accounted for the cluster design in their analyses, we will calculate the trials' effective sample sizes to account for the effect of clustering in data. When one or more cluster-RCT reports RRs adjusted for clustering, we will compute cluster-adjusted SEs for the other trials. When none of the cluster-RCTs provide cluster-adjusted RRs, we will adjust the sample size for clustering. We will divide, by the estimated design effects (DE), the number of events and number evaluated for dichotomous outcomes and the number evaluated for continuous outcomes, where DE = 1 + ((average cluster size 1) * ICC). The derivation of the estimated ICCs and DEs will be reported. We will utilize the intra-cluster correlation coefficient (ICC), derived from the trial (if available), or from another source (e.g., using the ICCs derived from other, similar trials) and then calculate the design effect with the formula provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). If this approach is used, we will report it and undertake sensitivity analysis to investigate the effect of variations in ICC. Studies with more than two treatment groups If we identify studies with more than two intervention groups (multi-arm studies), where possible we will combine groups to create a single pair-wise comparison or use the methods set out in the Cochrane Handbook to avoid double counting study participants (Higgins 2021). For the subgroup analyses, when the control group was shared by two or more study arms, we will divide the control group (events and total population) over the number of relevant subgroups to avoid double counting the participants. Trials with several study arms can be included more than once for different comparisons. Cross-over trials From cross-over trials, we will consider the first period of measurement only and will analyze the results together with parallel-group studies. Multiple outcome events In several outcomes, a participant might experience more than one outcome event during the trial period. For all outcomes, we will extract the number of participants with at least one event. Dealing with missing data We will contact the trial authors if the available data are unclear, missing, or reported in a format that is different from the format needed. We aim to perform a 'per protocol' or 'as observed' analysis; otherwise, we will perform a complete case analysis. This means that for treatment failure, we will base the analyses on the participants who received treatment and the number of participants for which there was an inability to clear malarial parasitaemia or prevent recrudescence after administration of an antimalarial medicine reported in the studies. Assessment of heterogeneity Heterogeneity in the results of the trials will be assessed by visually examining the forest plot to detect non-overlapping CIs, using the Chi2 test of heterogeneity (where a P value of less than 0.1 indicates statistical significance) and the I2 statistic of inconsistency (with a value of greater than 50% denoting moderate levels of heterogeneity). When statistical heterogeneity is present, we will investigate the reasons for it, using subgroup analysis. Assessment of reporting biases We will construct a funnel plot to assess the effect of small studies for the main outcome (when including more than 10 trials). Data synthesis The primary analysis will include all eligible studies that provide data regardless of the overall risk of bias as assessed by the RoB2 tool. Analyses will be conducted using Review Manager 5.4 (Review Manager 2020). Cluster-RCTs will be included in the main analysis after adjustment for clustering (see the previous section on cluster-RCTs). The meta-analysis will be performed using the Mantel-Haenszel random-effects model or the generic inverse variance method (when adjustment for clustering is performed by adjusting SEs), as appropriate. Subgroup analysis and investigation of heterogeneity The overall risk of bias will not be used as the basis in conducting our subgroup analyses. However, where data are available, we plan to conduct the following subgroup analyses, independent of heterogeneity. Dose of folic acid supplementation: higher doses (4 mg or more, daily) versus lower doses (less than 4 mg, daily). Moderate-severe anaemia at baseline (mean haemoglobin of participants in a trial at baseline below 100 g/L for pregnant women and children aged six to 59 months, and below 110 g/L for other populations) versus normal at baseline (mean haemoglobin above 100 g/L for pregnant women and children aged six to 59 months, and above 110 g/L for other populations). Antimalarial drug resistance to parasite: known resistance versus no resistance versus unknown/mixed/unreported parasite resistance. Folate status at baseline: Deficient (e.g. RBC folate concentration of less than 305 nmol/L, or serum folate concentration of less than 7nmol/L) and Insufficient (e.g. RBC folate concentration from 305 to less than 906 nmol/L, or serum folate concentration from 7 to less than 25 nmol/L) versus Sufficient (e.g. RBC folate concentration above 906 nmol/L, or serum folate concentration above 25 nmol/L). Presence of anaemia at baseline: yes versus no. Mandatory fortification status: yes, versus no (voluntary or none). We will only use the primary outcomes in any subgroup analyses, and we will limit subgroup analyses to those outcomes for which three or more trials contributed data. Comparisons between subgroups will be performed using Review Manager 5.4 (Review Manager 2020). Sensitivity analysis We will perform a sensitivity analysis, using the risk of bias as a variable to explore the robustness of the findings in our primary outcomes. We will verify the behaviour of our estimators by adding and removing studies with a high risk of bias overall from the analysis. That is, studies with a low risk of bias versus studies with a high risk of bias. Summary of findings and assessment of the certainty of the evidence For the assessment across studies, we will use the GRADE approach, as outlined in (Schünemann 2021). We will use the five GRADE considerations (study limitations based on RoB2 judgements, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence as it relates to the studies which contribute data to the meta-analyses for the primary outcomes. The GRADEpro Guideline Development Tool (GRADEpro) will be used to import data from Review Manager 5.4 (Review Manager 2020) to create 'Summary of Findings' tables. The primary outcomes for the main comparison will be listed with estimates of relative effects, along with the number of participants and studies contributing data for those outcomes. These tables will provide outcome-specific information concerning the overall certainty of evidence from studies included in the comparison, the magnitude of the effect of the interventions examined, and the sum of available data on the outcomes we considered. We will include only primary outcomes in the summary of findings tables. For each individual outcome, two review authors (KSC, LFY) will independently assess the certainty of the evidence using the GRADE approach (Balshem 2011). For assessments of the overall certainty of evidence for each outcome that includes pooled data from included trials, we will downgrade the evidence from 'high certainty' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias).
Topics: Child; Infant; Pregnancy; Infant, Newborn; Female; Humans; Child, Preschool; Antimalarials; Sulfadoxine; Pyrimethamine; Folic Acid Antagonists; Birth Weight; Parasitemia; Vitamins; Folic Acid; Anemia; Neural Tube Defects; Dietary Supplements; Iron; Recurrence
PubMed: 36321557
DOI: 10.1002/14651858.CD014217 -
Archives of Pathology & Laboratory... Oct 2020The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation...
CONTEXT.—
The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation dysfunction is a hallmark in patients with COVID-19. Fulminant thrombotic complications emerge as critical issues in patients with severe COVID-19.
OBJECTIVE.—
To present a review of the literature and discuss the mechanisms of COVID-19 underlying coagulation activation and the implications for anticoagulant and thrombolytic treatment in the management of COVID-19.
DATA SOURCES.—
We performed a systemic review of scientific papers on the topic of COVID-19, available online via the PubMed NCBI, medRxiv, and Preprints as of May 15, 2020. We also shared our experience on the management of thrombotic events in patients with COVID-19.
CONCLUSIONS.—
COVID-19-associated coagulopathy ranges from mild laboratory alterations to disseminated intravascular coagulation (DIC) with a predominant phenotype of thrombotic/multiple organ failure. Characteristically, high D-dimer levels on admission and/or continuously increasing concentrations of D-dimer are associated with disease progression and poor overall survival. SARS-CoV-2 infection triggers the immune-hemostatic response. Drastic inflammatory responses including, but not limited to, cytokine storm, vasculopathy, and NETosis may contribute to an overwhelming activation of coagulation. Hypercoagulability and systemic thrombotic complications necessitate anticoagulant and thrombolytic interventions, which provide opportunities to prevent or reduce "excessive" thrombin generation while preserving "adaptive" hemostasis and bring additional benefit via their anti-inflammatory effect in the setting of COVID-19.
Topics: Betacoronavirus; Blood Coagulation Disorders; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Thrombosis
PubMed: 32551814
DOI: 10.5858/arpa.2020-0324-SA -
Injury Oct 2019Sustained changes in resuscitation and transfusion management have been observed since the turn of the millennium, along with an ongoing discussion of surgical... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sustained changes in resuscitation and transfusion management have been observed since the turn of the millennium, along with an ongoing discussion of surgical management strategies. The aims of this study are threefold: a) to evaluate the objective changes in resuscitation and mass transfusion protocols undertaken in major level I trauma centers; b) to summarize the improvements in diagnostic options for early risk profiling in multiply injured patients and c) to assess the improvements in surgical treatment for acute major fractures in the multiply injured patient.
METHODS
I. A systematic review of the literature (comprehensive search of the MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases) and a concomitant data base (from a single Level I center) analysis were performed. Two authors independently extracted data using a pre-designed form. A pooled analysis was performed to determine the changes in the management of polytraumatized patients after the change of the millennium. II. A data base from a level I trauma center was utilized to test any effects of treatment changes on outcome.
INCLUSION CRITERIA
adult patients, ISS > 16, admission < less than 24 h post trauma. Exclusion: Oncological diseases, genetic disorders that affect the musculoskeletal system. Parameters evaluated were mortality, ICU stay, ICU complications (Sepsis, Pneumonia, Multiple organ failure).
RESULTS
I. From the electronic databases, 5141 articles were deemed to be relevant. 169 articles met the inclusion criteria and a manual review of reference lists of key articles identified an additional 22 articles. II. Out of 3668 patients, 2694 (73.4%) were male, the mean ISS was 28.2 (SD 15.1), mean NISS was 37.2 points (SD 17.4 points) and the average length of stay was 17.0 days (SD 18.7 days) with a mean length of ICU stay of 8.2 days (SD 10.5 days), and a mean ventilation time of 5.1 days (SD 8.1 days). Both surgical management and nonsurgical strategies have changed over time. Damage control resuscitation, dynamic analyses of coagulopathy and lactate clearance proved to sharpen the view of the worsening trauma patient and facilitated the prevention of further complications. The subsequent surgical care has become safer and more balanced, avoiding overzealous initial surgeries, while performing early fixation, when patients are physiologically stable or rapidly improving. Severe chest trauma and soft tissue injuries require further evaluation.
CONCLUSIONS
Multiple changes in management (resuscitation, transfusion protocols and balanced surgical care) have taken place. Moreover, improvement in mortality rates and complications associated with several factors were also observed. These findings support the view that the management of polytrauma patients has been substantially improved over the past 3 decades.
Topics: Blood Transfusion; Fracture Fixation; Fractures, Bone; Hospitalization; Humans; Injury Severity Score; Multiple Organ Failure; Multiple Trauma; Practice Guidelines as Topic; Resuscitation; Time-to-Treatment; Trauma Centers
PubMed: 31558277
DOI: 10.1016/j.injury.2019.09.021 -
Cells May 2023Coronavirus disease 2019 (COVID-19) is a viral infection caused by SARS-CoV-2 that induces a generalized inflammatory state. Organokines (adipokines, osteokines,... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a viral infection caused by SARS-CoV-2 that induces a generalized inflammatory state. Organokines (adipokines, osteokines, myokines, hepatokines, and cardiokines) can produce beneficial or harmful effects in this condition. This study aimed to systematically review the role of organokines on COVID-19. PubMed, Embase, Google Scholar, and Cochrane databases were searched, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and 37 studies were selected, comprising more than 2700 individuals infected with the virus. Among COVID-19 patients, organokines have been associated with endothelial dysfunction and multiple organ failure due to augmented cytokines and increased SARS-CoV-2 viremia. Changes in the pattern of organokines secretion can directly or indirectly contribute to aggravating the infection, promoting immune response alterations, and predicting the disease progression. These molecules have the potential to be used as adjuvant biomarkers to predict the severity of the illness and severe outcomes.
Topics: Humans; COVID-19; SARS-CoV-2
PubMed: 37408184
DOI: 10.3390/cells12101349 -
Pediatrics Jan 2022Multiple scores exist to characterize organ dysfunction in children.
CONTEXT
Multiple scores exist to characterize organ dysfunction in children.
OBJECTIVE
To review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020.
STUDY SELECTION
Studies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes.
DATA EXTRACTION
Data were abstracted into a standard data extraction form by a task force member.
RESULTS
Of 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially.
LIMITATIONS
While scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely.
CONCLUSIONS
The multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children.
Topics: Child; Critical Illness; Humans; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis
PubMed: 34970683
DOI: 10.1542/peds.2021-052888D -
The Journal of Trauma and Acute Care... May 2023Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time.
METHODS
Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable.
RESULTS
The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1-17.2%) in Denver score >3, 12.7% (95% CI, 9.3-16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12-45.1%) in Denver score >8, 25.6% (95% CI, 10.4-40.7%) in Goris score >4, 29.9% (95% CI, 14.9-45%) in Marshall score >5, 20.3% (95% CI, 9.4-31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33-44.3%) in SOFA score >3, 55.1% (95% CI, 49.7-60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7-40.8%) in SOFA score >5.
CONCLUSION
The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered.
LEVEL OF EVIDENCE
Systematic Review and Meta-analysis; Level III.
Topics: Humans; Adult; Multiple Organ Failure; Incidence; Multiple Trauma; Organ Dysfunction Scores; Wounds, Nonpenetrating
PubMed: 36809374
DOI: 10.1097/TA.0000000000003923 -
Revista Brasileira de Ginecologia E... Jul 2016Purpose Pelvic organ prolapse (POP) is a major health issue worldwide, affecting 6-8% of women. The most affected site is the anterior vaginal wall. Multiple... (Meta-Analysis)
Meta-Analysis Review
Purpose Pelvic organ prolapse (POP) is a major health issue worldwide, affecting 6-8% of women. The most affected site is the anterior vaginal wall. Multiple procedures and surgical techniques have been used, with or without the use of vaginal meshes, due to common treatment failure, reoperations, and complication rates in some studies. Methods Systematic review of the literature and meta-analysis regarding the use of vaginal mesh in anterior vaginal wall prolapse was performed. A total of 115 papers were retrieved after using the medical subject headings (MESH) terms: 'anterior pelvic organ prolapse OR cystocele AND surgery AND (mesh or colporrhaphy)' in the PubMed database. Exclusion criteria were: follow-up shorter than 1 year, use of biological or absorbable meshes, and inclusion of other vaginal wall prolapses. Studies were put in a data chart by two independent editors; results found in at least two studies were grouped for analysis. Results After the review of the titles by two independent editors, 70 studies were discarded, and after abstract assessment, 18 trials were eligible for full text screening. For final screening and meta-analysis, after applying the Jadad score (> 2), 12 studies were included. Objective cure was greater in the mesh surgery group (odds ratio [OR] = 1,28 [1,07-1,53]), which also had greater blood loss (mean deviation [MD] = 45,98 [9,72-82,25]), longer surgery time (MD = 15,08 [0,48-29,67]), but less prolapse recurrence (OR = 0,22 [01,3-0,38]). Dyspareunia, symptom resolution and reoperation rates were not statistically different between groups. Quality of life (QOL) assessment through the pelvic organ prolapse/urinary incontinence sexual questionnaire (PISQ-12), the pelvic floor distress inventory (PFDI-20), the pelvic floor impact questionnaire (PFIQ-7), and the perceived quality of life scale (PQOL) was not significantly different. Conclusions Anterior vaginal prolapse mesh surgery has greater anatomic cure rates and less recurrence, although there were no differences regarding subjective cure, reoperation rates and quality of life. Furthermore, mesh surgery was associated with longer surgical time and greater blood loss. Mesh use should be individualized, considering prior history and risk factors for recurrence.
Topics: Female; Gynecologic Surgical Procedures; Humans; Pelvic Organ Prolapse; Surgical Mesh
PubMed: 27472812
DOI: 10.1055/s-0036-1585074