Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis

IntroductionHydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection.MethodsWe searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model.ResultsPooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00–1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31–1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55–4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58–1.88).ConclusionsHCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.     

SARS-CoV-2 pharmacologic therapies and their safety/effectiveness according to level of evidence

IntroductionThere is a pressing need for COVID-19 transmission control and effective treatments. We aim to evaluate the safety and effectiveness of SARS-CoV-2 pharmacologic therapies as of August 2, 2020 according to study level of evidence.MethodsPubMed, ScienceDirect, Cochrane Library, JAMA Network and PNAS were searched. The following keywords were used: ((COVID-19) OR (SARS-CoV-2)) AND ((((((therapeutics) OR (treatment)) OR (vaccine)) OR (hydroxychloroquine)) OR (antiviral)) OR (prognosis)). Results included peer-reviewed studies published in English.Results15 peer-reviewed articles met study inclusion criteria, of which 14 were RCTs and one was a systematic review with meta-analysis. The following pharmacologic therapies were evaluated: chloroquine (CQ), hydroxychloroquine (HCQ), antivirals therapies, plasma therapy, anti-inflammatories, and a vaccine.ConclusionAccording to level 1 evidence reviewed here, the most effective SARS-Co-V-2 pharmacologic treatments include remdesivir for mild to severe disease, and a triple regimen therapy consisting of lopinavir-ritonavir, ribavirin and interferon beta-1b for mild to moderate disease. Also, dexamethasone significantly reduced mortality in those requiring respiratory support. However, there is still a great need for detailed level 1 evidence on pharmacologic therapies.     

Impact of colchicine on mortality and morbidity in COVID-19: a systematic review

IntroductionColchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate “cytokine storm” and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies.ObjectiveTo evaluate the role of colchicine on morbidity and mortality in COVID-19 patients.MethodsThis systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated for risk of bias (ROB) using the Revised Cochrane ROB tool for randomised controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for case-control and cohort studies.ResultsFour RCTs and four observational studies were included in the final analysis. One study evaluated colchicine in outpatients, while all others evaluated inpatient use of colchicine. There was significant variability in treatment protocols for colchicine and standard of care in all studies. A statistically significant decrease in all-cause mortality was observed in three observational studies. The risk of mechanical ventilation was significantly reduced only in one observational study. Length of hospitalisation was significantly reduced in two RCTs. Risk for hospitalisation was not significantly decreased in the study evaluating colchicine in outpatients. Very few studies had low risk of bias.ConclusionBased on the available data, colchicine shall not be recommended to treat COVID-19. Further high-quality and multi-center RCTs are required to assess the meaningful impact of this drug in COVID-19.

KEY MESSAGES

• Colchicine, an anti-inflammatory agent has demonstrated anti-viral properties in in-vitro studies by degrading the microtubules, as well as by inhibiting the production of pro-inflammatory cytokines.
• Colchicine has been studied as a potential therapeutic option for COVID-19, with variable results.
• Until further research can establish the efficacy of colchicine in COVID-19, the use of colchicine in COVID-19 shall be restricted to clinical trials.

     

Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort

ObjectiveHydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19.MethodsThis retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021.ResultsAlmost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty.ConclusionsThis study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.     

Effect of Pulmonary Rehabilitation Approaches on Dyspnea,Exercise Capacity,Fatigue, Lung Functions,and Quality of Life in Patients With COVID-19: A Systematic Review and Meta-analysis

ObjectiveTo qualitatively synthesize and quantitatively evaluate the effect of pulmonary rehabilitation (PR) on dyspnea, lung functions, fatigue, exercise capacity, and quality of life (QoL) in patients with COVID-19.Data SourcesPubMed, Web of Science, and Cochrane databases were searched from January 2020 to April 2022.Data SelectionRandomized controlled trials (RCTs) assessing the effect of PR on dyspnea, lung functions, fatigue, exercise capacity, and QoL in patients with COVID-19.Data ExtractionThe mean difference (MD) and a 95% CI were estimated for all the outcome measures using random effect models. The following data were extracted by 2 independent reviewers: (1) first author; (2) publication year; (3) nationality; (4) number of patients included (5) comorbidities; (6) ventilatory support; (7) length of inpatient stay; (8) type of PR; (9) outcome measures; and (10) main findings. The risk of bias was evaluated using the cochrane risk of bias tool.Data SynthesisA total of 8 RCTs involving 449 participants were included in the review. PR was found to be significantly effective in improving dyspnea (5 studies, SMD -2.11 [95% CI, -2.96 to -1.27; P<.001]) and exercise capacity (MD 65.85 m [95% CI, 42.86 to 88.83; P<.001]) in patients with both acute and chronic COVID-19 with mild to severe symptoms, whereas fatigue (MD -2.42 [95% CI, -2.72 to -2.11, P<.05]) and lung functions (MD 0.26 L [95% CI, 0.04 to 0.48, P<.05]) were significantly improved in acute COVID-19 patients with mild symptoms. The effect of PR on QoL was inconsistent across studies. PR was found to be safe and feasible for patients with COVID-19.ConclusionEvidence from studies indicates that PR program is superior to no intervention in improving dyspnea, exercise capacity, lung functions, and fatigue in patients with COVID-19. PR appears to be safe and beneficial for both acute and chronic COVID-19 patients.     

Chloroquine and hydroxychloroquine provoke arrhythmias at concentrations higher than those clinically used to treat COVID‐19: A simulation study

AbstractThe risk of fatal arrhythmias is the major concern for using chloroquine (CQ) or hydroxychloroquine (HCQ) to treat coronavirus disease 2019 (COVID‐19), but the reported number of life‐threatening arrhythmic events or deaths is relatively small. The objective of this study was to assess the arrhythmogenic risk of these two drugs using a multiscale heart simulation, which allows testing even at high concentrations, including those that cause fatal arrhythmias. We measured the inhibitory action of CQ, HCQ, and HCQ with 30 μM azithromycin (AZ) on six ion currents (fast [INa] and late [INa,L] components of the sodium current, L‐type calcium current [ICa,L], rapid [IKr/hERG], and slow [IKs] components of delayed rectifier potassium, and inward rectifier potassium [IK1]) over a wide range of concentrations using the automated patch‐clamp system. Using the concentration–inhibition relationship that was thus obtained, we simulated the drug effects while increasing the concentration until the life‐threatening arrhythmia, torsade de pointes (TdP), was observed. The obtained threshold concentrations for TdP were 12.5, 35, and 22.5 μM for CQ, HCQ, and HCQ with AZ, respectively. Adding therapeutic concentrations of mexiletine or verapamil successfully prevented the occurrence of TdP, and verapamil was more effective. CQ, HCQ, and HCQ with AZ thresholds for TdP were larger than both antiviral concentrations that were reported by in vitro experiments and free plasma concentrations that were attained by the clinically used dosage. The current simulation data provided a safety margin to the currently used clinical dose for CQ and HCQ/AZ. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Despite the potent in vitro antiviral effect, clinical trials have failed to show the therapeutic effects of chloroquine (CQ) and hydroxychloroquine (HCQ)/azithromycin (AZ) to treat coronavirus disease 2019. Torsadogenic potentials may limit the dosage of these drugs, but the reported incidence of fatal arrhythmias is rare.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Our objective was to assess the arrhythmogenicity of CQ and HCQ/AZ over a wide range of drug concentrations using a multiscale heart simulation.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Our study showed that CQ and HCQ/AZ do not induce fatal arrhythmias even at concentrations much higher than in vitro antiviral half‐maximal effective concentration (EC₅₀) values at which QT prolongation exceeds 150 ms. We also found that estimated free plasma concentrations of CQ and HCQ/AZ achieved by currently used dosing protocols are lower than the antiviral EC₅₀ for these drugs.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Our simulation data provided a safety margin to the currently used clinical dose for CQ and HCQ/AZ.     

Therapeutic effects and safety of oral Chinese patent medicine for COVID-19: A rapid systematic review and meta-analysis of randomized controlled trials

IntroductionChinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19.MethodsWe included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.ResultsSeven RCTs including 1079 participants were identified. The overall bias was assessed as “-high risk of bias” for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04–1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 – 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea.ConclusionLow-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.     

Mortality,viral clearance,and other clinical outcomes of hydroxychloroquine in COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Many meta‐analyses have been published about the efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID‐19). Most of them included observational studies, and few have assessed HCQ as a prophylaxis or evaluated its safety profile. We searched multiple databases and preprint servers for randomized controlled trials (RCTs) that assessed HCQ for the treatment or prevention of COVID‐19. We summarized the effect of HCQ on mortality, viral clearance, and other clinical outcomes. Out of 768 papers screened, 21 RCTs with a total of 14,138 patients were included. A total of 9 inpatient and 3 outpatient RCTs assessed mortality in 8596 patients with a pooled risk difference of 0.01 (95% confidence interval [CI] 0.00–0.03, I ² = 1%, p = 0.07). Six studies assessed viral clearance at 7 days with a pooled risk ratio (RR) of 1.11 (95% CI 0.86–1.42, I ² = 61%, p = 0.44) and 5 studies at 14 days with a pooled RR of 0.96 (95% CI 0.89–1.04, I ² = 0%, p = 0.34). Several trials showed no significant effect of HCQ on other clinical outcomes and. Five prevention RCTs with 5012 patients found no effect of HCQ on the risk of acquiring COVID‐19. Thirteen trials showed that HCQ was associated with increased risk of adverse events. We observed, with high level of certainty of evidence, that HCQ is not effective in reducing mortality in patients with COVID‐19. Lower certainty evidence also suggests that HCQ neither improves viral clearance and other clinical outcomes, nor prevents COVID‐19 infection in patients with high‐risk exposure. HCQ is associated with an increased rate of adverse events.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

• Antimalarial agents have been shown to exert in vitro anti severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) activity, with conflicting clinical results. The data of the published meta‐analyses came mainly from observational studies, hence limiting the reliability of their findings.

WHAT QUESTION DID THIS STUDY ADDRESS?

• This study explores the efficacy and safety of hydroxychloroquine (HCQ)in coronavirus disease 2019 (COVID‐19) disease, using data from a large number of randomized clinical trials.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

• Our study provides conclusive evidence that HCQ has no benefit in the treatment or prevention of COVID‐19 disease. HCQ therapy was also associated with higher incidence of adverse events.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

• Our findings will stimulate further mechanistic studies to resolve the contradictory findings of clinical and in vitro findings.

     

Ethical review of off-label drugs during the COVID-19 pandemic

High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019 (COVID-19) pandemic and ensure people’s health and safety. Chloroquine (CQ) and hydroxychloroquine (HCQ) have received much attention. This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards, improving review efficiency, ensuring the rights and interests of subjects and that ethics committees conduct independent reviews, and achieving full ethics supervision of research conducted during an emergency. Research must be both rigorous and prudent to ensure the best outcome, with the maximization of benefits as the core principle. Standardization of the application, implementation and ethical review processes are needed to prevent unnecessary risk.     

The reporting quality and risk of bias of randomized controlled trials of acupuncture for migraine: Methodological study based on STRICTA and RoB 2.0

ObjectivesTo investigate the reporting quality and risk of bias of randomized controlled trials (RCTs) of acupuncture for migraine, to facilitate and improve the quality of RCTs of acupuncture for migraine.MethodsThe Cochrane Library, PubMed and EMBASE were searched from inception to June 11, 2019 using a comprehensive search strategy. The reporting quality and risk of bias of included RCTs were independently evaluated by two investigators using STRICTA and RoB 2.0. Any disagreement was resolved by a third investigator.ResultsA total of 28 eligible RCTs were published in 24 academic journals from 1994 to 2018. Based on STRICTA, four sub-items including “details of other interventions’’ (1/28, 4 %), “setting and context of treatment” (9/28, 32 %), “the extent to which treatment was varied” (11/28, 39 %), and “number of needle insertions per subject per session” (13/28, 46 %), showed low reporting quality. A total of 32 different outcomes were reported in 28 RCTs, and based on RoB 2.0, nine (9/28, 32 %) RCTs were judged to be high RoB, three of which were owing to deviations from intended interventions; 11(11/28, 39 %) RCTs elicited some concerns; and eight (8/28, 29 %) RCTs were low RoB for their outcomes.ConclusionsThe reporting quality and risk of bias of RCTs of acupuncture for migraine remain suboptimal. Therefore, all stakeholders should make a contribution to improve the quality of RCTs of acupuncture for migraine using STRICTA and RoB 2.0, while not limiting this approach solely to studies on migraine, using STRICTA and RoB 2.0 tools.     

Intracranial hemorrhage in patients treated for SARS-CoV-2 with extracorporeal membrane oxygenation: A systematic review and meta-analysis

BackgroundExtracorporeal membrane oxygenation (ECMO) is routinely used in patients with severe respiratory failure and has been increasingly needed during the COVID-19 pandemic. In patients treated with ECMO, significant intracranial hemorrhage (ICH) risk exists due to circuit characteristics, anticoagulation, and disease characteristics. ICH risk may be substantially higher in COVID-19 patients than patients treated with ECMO for other indications.MethodsWe systematically reviewed current literature regarding ICH during ECMO treatment of COVID-19. We utilized Embase, MEDLINE, and Cochrane Library databases. Meta-analysis was performed for included comparative studies. Quality assessment was performed using MINORS criteria.ResultsA total of 54 studies with 4000 ECMO patients were included, all retrospective. Risk of bias was increased via MINORS score primarily due to retrospective designs. ICH was more likely in COVID-19 patients (RR 1.72, 95% CI 1.23, 2.42). Mortality among COVID patients on ECMO with ICH was 64.0%, compared with 41% in patients without ICH (RR1.9, 95% 1.44, 2.51).ConclusionThis study suggests increased hemorrhage rates in COVID-19 patients on ECMO compared to similar controls. Hemorrhage reduction strategies may include atypical anticoagulants, conservative anticoagulation strategies, or biotechnology advances in circuit design and surface coatings.     

Mindfulness- and Acceptance-Based Interventions for Symptom Reduction in Individuals With Multiple Sclerosis: A Systematic Review and Meta-Analysis

ObjectiveTo examine the effects of mindfulness- and acceptance-based interventions (MABIs) on reducing symptoms in individuals with multiple sclerosis (MS).Data SourcesA comprehensive search was conducted within the PubMed, CINAHL, PsycINFO, and SCOPUS databases for articles published from inception to July 3, 2020.Study SelectionRandomized controlled trials (RCTs) were included if MABIs were provided to individuals with MS exclusively, with reported pre-and posttest results in symptoms of depression, anxiety, stress, fatigue, or pain.Data ExtractionCharacteristics of the included RCTs and data for meta-analysis were extracted. The quality of the included RCTs was assessed using the Cochrane Collaboration risk of bias tool.Data SynthesisA random effects model with the inverse variance method was used with effect size reported as standardized mean difference. Heterogeneity was assessed using the I² statistic.ResultsTwenty-three RCTs met the eligibility criteria. Meta-analyses found large effects of MABIs on reducing depressive symptoms, anxiety, stress, and pain, as well as a moderate effect of MABIs on reducing fatigue at the immediate posttest. Large effects of MABIs on reducing depressive symptoms, anxiety, and stress at follow-up were also found, whereas a moderate effect on reducing fatigue was found at follow-up. There was no significant effect of MABIs on reducing pain at follow-up.ConclusionsFewer studies were included in meta-analyses for pain at the immediate posttest and follow-up and stress and fatigue at follow-up. The overall risk of bias was unclear. Future high-quality studies with follow-up evaluations are needed to support effects of MABIs on reducing symptoms in individuals with MS and examine intervention features that increase and maintain effects.     

Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum,in agreement with its physicochemical properties

The 4-aminoquinoline drug hydroxychloroquine (HCQ) is reported to be as active as chloroquine (CQ) against falciparum malaria, and less toxic. Existing prophylactic regimens for areas where there is CQ-resistant malaria recommend CQ with proguanil as an alternative where none of the three preferred regimens (atovaquone-proguanil, doxycycline or mefloquine) is thought suitable. In such cases, toxicity is likely when CQ-proguanil is administered to persons being treated for autoimmune disease with daily HCQ. The question therefore arises whether in such circumstances HCQ could effectively replace the CQ component of the prophylactic combination. We confirmed similar activity of CQ and HCQ against CQ-sensitive Plasmodium falciparum, but found that whereas HCQ in vitro was 1.6 times less active than CQ in a CQ-sensitive isolate, it was 8.8 times less active in a CQ-resistant isolate. The result can also be predicted from an analysis of the physicochemical properties of CQ and HCQ. To give limited protective effect similar to 300 mg CQ base weekly against CQ-resistant P. falciparum would demand daily doses of HCQ above the recommended safe level. These observations contraindicate the use of HCQ in prophylaxis or treatment of CQ-resistant falciparum malaria. Where CQ-proguanil prophylaxis is the only option available in a patient on high-dose HCQ treatment, visiting a CQ-resistant area, replacement of the anti-inflammatory regimen by a daily CQ course at a suitable dose should be considered.     

Exercise for Depressive Symptoms in Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo evaluate the efficacy of physical exercise in improving depressive symptoms in Parkinson disease (PD).Data Source and Study SelectionWe conducted a systematic review of randomized controlled trials (RCTs) following a prespecified protocol guidance (PROSPERO CRD42021243142). Two independent authors searched for studies in MEDLINE, Cochrane Register of Controlled Trials, Physiotherapy Evidence Database, Embase, PsycINFO, and Sports Discus from database inception to June 2022.Data ExtractionTwo independent authors extracted the data and evaluated the risk of bias using the revised Cochrane risk of bias tool. We performed random-effects meta-analyses and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Data SynthesisA total of 36 RCTs met the inclusion criteria, 14 of which were pooled in the quantitative synthesis. Depression symptomatology significantly decreased in the exercise group compared with usual care (standardized mean difference [SMD], ?0.49; 95% confidence interval [CI], ?0.74 to ?0.24; very low quality of evidence; 14 RCTs; 961 participants). Physical exercise also improved patients’ quality of life (SMD, ?0.51; 95% CI, ?0.81 to ?0.21; 7 RCTs; 485 participants). As for acceptability, we did not find any difference between exercise and usual care (relative risk, 1.01; 95% CI, 0.97 to 1.05; 12 RCTs; 1048 participants). We judged all the studies except 2 to be at high risk of bias.ConclusionsResults from our systematic review identify physical activity as a viable option to reduce depressive symptoms in PD. Future clinical practice guidelines should consider physical exercise in their recommendations for depression symptomatology reduction in people with PD.     

Acupuncture for the treatment of childhood anorexia: A systematic review and meta-analysis

ObjectivesChildhood anorexia, among the commonest symptoms of children, involved long-term loss of appetite/decreased food intake and refusal to try or eat certain foods. Acupuncture is increasingly popular in childhood anorexia due to the side effects and dissatisfaction of conventional treatment, but, the efficacy and safety of acupuncture for childhood anorexia have not been reviewed systematically.MethodsFrom 12 electronic databases, randomized controlled trials (RCTs) assessing acupuncture for childhood anorexia were identified in June 2021, with posttreatment improvement in clinical symptoms of anorexia as the primary outcome. A meta-analysis was conducted if two or more studies used the same interventions or same outcome measures. The risk of bias and quality of evidence were evaluated.ResultsA total of 32 RCTs with 3518 participants were included. When acupuncture was used as monotherapy or adjunctive therapy, the total effectiveness rate based on anorexia symptoms, hemoglobin levels, abdominal subcutaneous fat, and body weight significantly improved. However, results in nutritional indices were inconsistent. The recurrence rate of anorexia was significantly lower in the acupuncture group. No serious adverse events in relation to acupuncture were reported. in general, the risk of bias of the included studies was unclear and the quality of evidence for the main findings was low to moderate.ConclusionsAcupuncture may improve symptoms of childhood anorexia without serious adverse events. However, because of the low methodological quality and quality of evidence in existing reports, further high-quality clinical trials are needed to conclusively establish the efficacy and safety of this treatment.     

Efficacy and Safety of Blood Derivative Therapy for Patients with COVID-19: A Systematic Review and Meta-Analysis

BackgroundThe outbreak of COVID-19 has resulted in more than 200 million infections and 4 million deaths. The blood derivative therapy represented by intravenous immunoglobulin (IVIG) and convalescent plasma (CP) therapy may be the promising therapeutics for COVID-19.MethodsA systematic article search was performed for eligible studies published up to August 3, 2021, through the PubMed, Embase, Cochrane Library. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated.ResultsA total of 5 IVIG therapy and 13 CP therapy randomized controlled trials were included with a sample size of 13,696 subjects diagnosed with COVID-19. IVIG could reduce the mortality compared with the control group (RR 0.65, 95% CI: 0.46–0.93, p = 0.02). The use of CP did not effectively reduce the mortality (RR 0.97, 95% CI: 0.91–1.03, p = 0.38), the length of hospital stay (MD −0.47, 95% CI: −4.13 to 3.20, p = 0.80), and the mechanical ventilation use (RR = 0.98, 95% CI: 0.89–1.07, p = 0.62) of the patients with COVID-19. Treatment with IVIG or CP was not significantly associated with an increase in reported adverse events (RR 1.07, 95% CI: 0.94–1.22, p = 0.28).ConclusionsTreatment with IVIG could be effective and safe to improve survival for patients with COVID-19. But the benefit of CP in the treatment of COVID-19 is limited. The certainty of the evidence was moderate for all outcomes.     

Are movement-based classification systems more effective than therapeutic exercise or guideline based care in improving outcomes for patients with chronic low back pain? A systematic review

Objectives: The purpose of this systematic review was to determine if movement-based classification (MBC) systems are more effective than therapeutic exercise or guideline-based care (GBC) in improving outcomes in patients with low back pain (LBP) based upon randomized clinical trials (RCT) with moderate to high methodological quality and low to moderate risk of bias.

Methods: The search strategy was developed by a librarian experienced in systematic review methodology and peer reviewed by a second research librarian. The following databases were searched from their inception to May 17, 2018: PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. The identified RCTs with a PEDro score of ≥6 were screened and assessed for risk of bias by two blinded individual reviewers using Covidence.

Results: Seven studies were identified that had moderate-to-high methodological quality. One of the studies was identified as having a high risk of bias. Of the six studies that remained, only one study reported finding a statistically significant difference at the immediate follow-up that was not clinically significant. There was no significance at 6 and 12 months.

Discussion: There is a paucity of moderate to high methodological quality RCTs with similar methodology that compare MBC to standard of care treatments for patients with LBP. Studies with moderate to high methodological quality that have a low risk of bias do not support MBCs as being superior to general exercise or GBC in the treatment of nonradicular LBP.

Level of Evidence: 1a     

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease

ObjectivesTo alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission.MethodsIn this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19.ResultsOf 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19.ConclusionOur study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.     

Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials

PurposeThe optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19.Materials and methodsWe conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered.ResultsOut of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90–1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61–1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21–0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08–2.53).ConclusionThis systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.