Telemedicine in Diabetic Foot Care: A Systematic Literature Review of Interventions and Meta-analysis of Controlled Trials

The care of individuals with diabetic foot ulcers is costly and requires multiple hospital visits. Inadequate care leads to serious complications and a high risk of lower extremity amputation. In this review, we aimed at evaluating whether telemedicine can be effective in diabetic foot patient care. We searched Medline through Embase and PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant studies, published up to April 2017. The studies were summarized and discussed in a narrative method and a meta-analysis of 2 controlled trials was conducted using the fixed-effects model. The main outcomes, assessed in the retrieved studies were the healing rate and satisfaction of patients and health care personnel. Most of the studies showed that implementing telemonitoring programs increased the rate of complete ulcer healing, while the patients were highly satisfied. Two trials providing data on 213 patients on telemedicine and 301 patients on usual care were included for meta-analysis. Subjects in telemedicine, as well as control groups had statistically similar healing time (43 vs 45 days; P = .83), healing time ratio adjusted for age (1 vs 1.4; P = .1), unhealed ulcers or loss to follow-up (3 of 20 vs 7 of 120; P = .13), and amputations (12 of 193 vs 14 of 182; P = .59). Subjects in the telemedicine group experienced a significantly higher mortality rate (8 of 193 vs 1 of 181; P = .0001) due to unexplained factors. No adverse events were attributed to using the telemedicine technology. The odds of complete ulcer healing were statistically similar between the telemedicine group and controls (odds ratio = 0.86; 95% CI = 0.57-1.33; P = .53). Telemedicine care is promising for the management of diabetic foot patients as the results were comparable with usual care. However, further large-scale studies need to be undertaken before it can be implemented widely.

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Cinacalcet Treatment Significantly Improves All-Cause and Cardiovascular Survival in Dialysis Patients: Results from a Meta-Analysis

Kidney & Blood Pressure Research ◽

10.1159/000504139 ◽

2019 ◽

Vol 44 (6) ◽

pp. 1327-1338 ◽

Cited By ~ 1

Author(s):

Yuan Zu ◽

Xiangxue Lu ◽

Jinghong Song ◽

Ling Yu ◽

Han Li ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Observational Studies ◽

Fixed Effects ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Fixed Effects Model ◽

Long Term Effects ◽

Dialysis Patients ◽

All Cause Mortality

Objective: To assess the long-term effects including all-cause mortality, cardiovascular mortality, and fracture incidence, of cinacalcet on secondary hyperparathyroidism (SHPT) in patients on dialysis. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to October 2018. Randomized controlled trials (RCTs) and cohort design prospective observational studies assessing cinacalcet for the treatment of SHPT in dialysis patients were included. Data extraction was independently completed by 2 authors who determined the methodological quality of the studies and extracted data in duplicate. Study-specific risk estimates were tested by using a fixed effects model. Results: A total of 14 articles with 38,219 participants were included, of which 10 RCTs with 7,471 participants and 4 prospective observational studies with 30,748 participants fulfilled the eligibility criteria. Compared with no cinacalcet, cinacalcet administration reduced all-cause mortality (relative risk [RR] 0.91, 95% CI 0.89–0.94, p < 0.001) and cardiovascular mortality (RR 0.92, 95% CI 0.89–0.95, p < 0.001), but it did not significantly reduce the incidence of fractures (RR 0.93, 95% CI 0.87–1.00, p = 0.05). Conclusions: The results of this meta-analysis indicated that the treatment of SHPT with cinacalcet may in fact reduce all-cause mortality and cardiovascular mortality among patients receiving maintenance dialysis.

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Efficacy and safety of daptomycin: systematic review and meta-analysis

Therapeutic Advances in Infectious Disease ◽

10.1177/2049936119886465 ◽

2019 ◽

Vol 6 ◽

pp. 204993611988646

Author(s):

María Teresa Rosanova ◽

David Bes ◽

Pedro Serrano-Aguilar ◽

Norma Sberna ◽

Estefania Herrera-Ramos ◽

...

Keyword(s):

Treatment Failure ◽

Fixed Effects ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Failure Rates ◽

Efficacy And Safety ◽

Fixed Effects Model ◽

Intention To Treat ◽

Central Register

Background: The aim of this study was to assess whether daptomycin is safer and more efficacious than comparators for the treatment of serious infection caused by gram-positive microorganisms. Methods: Electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify randomized controlled trials (RCTs) that assessed the efficacy and safety of daptomycin versus therapy with any other antibiotic comparator. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. Heterogeneity was assessed, and a random-effects or fixed-effects model, when appropriate, was used for estimates of risk ratio (RR). The primary outcome assessed was the risk of clinical treatment failure among the intention-to-treat population and the presence of any treatment related adverse event (AEs). Results: A total of seven trials fulfilled the inclusion criteria. Daptomycin treatment failure rates were no different to comparator regimens (RR = 0.96; CI 95% 0.86–1.06). No significantly different treatment related AEs were identified when comparing groups (RR = 0.91; CI 95% 0.83–1.01). Conclusions: No significant differences in treatment failure rates and safety were found using daptomycin or any of the comparators treatment.

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Efficacy of PD-1/PD-L1 inhibitor-based therapies in refractory microsatellite instability (MSI)-unselected metastatic colorectal cancer (mCRC): A network meta-analysis (NMA) of randomized controlled trials (RCTs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15048 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15048-e15048

Author(s):

Zi-xian Wang ◽

Yu-tong Chen ◽

Yi-xin Zhou ◽

Hao-xiang Wu ◽

Zhan-Hong Chen ◽

...

Keyword(s):

Fixed Effects ◽

Meta Analysis ◽

Best Supportive Care ◽

Controlled Trials ◽

Significant Heterogeneity ◽

Cochrane Central Register ◽

Fixed Effects Model ◽

Hazard Ratios ◽

Central Register ◽

Treatment Comparisons

e15048 Background: PD-1/PD-L1 inhibitor-based monotherapies and combination therapies are being investigated to challenge microsatellite stable (MSS) mCRC. This NMA aimed to assess the efficacy of anti-PD-1/PD-L1-based therapies against active comparators (regorafenib, trifiuridine+tipiracil, and fruquintinib [R/T/F]) and negative controls (placebo and best supportive care [P/BSC]) in patients with refractory MSI-unselected mCRC, which are predominantly MSS. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and major oncology websites for relevant RCTs comparing the above therapies with each other up to Feb 15, 2019. We used the frequentist NMA to evaluate hazard ratios (HRs) for pairwise treatment comparisons in terms of overall survival (OS). Results: Seven RCTs were included, totaling nine comparisons between five therapies (durvalumab+tremelimumab [anti-PD-L1+Tre] vs. P/BSC [n = 1], atezolizumab+cobimetinib [anti-PD-L1+Cobi] vs. R/T/F [n = 1], atezolizumab [anti-PD-L1-only] vs. R/T/F [n = 1], anti-PD-L1+Cobi vs. anti-PD-L1-only [n = 1], and R/T/F vs. P/BSC [n = 5]). No significant heterogeneity was detected in the NMA (P = 0.340 in Q test; I2= 11.6%). Compared to P/BSC, OS was significantly improved with anti-PD-L1+Tre (fixed-effects model HR, 0.72 [95% confidence interval, 0.54-0.96]; P = 0.014) and anti-PD-L1+Cobi (HR, 0.70 [0.50-0.98]; P = 0.018), but not with anti-PD-L1-only (HR, 0.83 [0.57-1.21]; P = 0.172). OS with anti-PD-L1+Tre and anti-PD-L1+Cobi did not significantly differ from that with R/T/F (P = 0.565 and P = 0.500, respectively). Conclusions: In refractory MSI-unselected mCRC, anti-PD-L1 monotherapy was ineffective but anti-PD-L1+Tre and anti-PD-L1+Cobi therapies exhibited efficacies comparable to that of R/T/F.

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Effectiveness of Multimodal Training on Functional Capacity in Frail Older People: A Meta-Analysis of Randomized Controlled Trials

Journal of Aging and Physical Activity ◽

10.1123/japa.2017-0188 ◽

2018 ◽

Vol 26 (3) ◽

pp. 407-418 ◽

Cited By ~ 8

Author(s):

Pedro Lopez ◽

Mikel Izquierdo ◽

Regis Radaelli ◽

Graciele Sbruzzi ◽

Rafael Grazioli ◽

...

Keyword(s):

Older People ◽

Fixed Effects ◽

Meta Analysis ◽

Maximum Strength ◽

Controlled Trials ◽

Cochrane Central Register ◽

Frail Older People ◽

Timed Up And Go ◽

Positive Effects ◽

Multimodal Training

In this meta-analysis, we investigated the effect of resistance training (RT) alone or included in a multimodal training on physical frailty outcomes, and whether different variables of RT prescription affect these outcomes. We identified 15 relevant studies searching through MEDLINE, Cochrane Central Register of Controlled Trials, SPORTDiscus, and PEDro database. Postintervention standardized mean difference scores were computed and combined using fixed effects meta-analysis. Analyses have shown positive effects of interventions on maximum strength, gait speed, and Timed Up and Go test. Further analyses have shown significant greater effect of shorter periods on maximum strength. Regarding RT prescription, percentage of one-repetition maximum showed significant effect on physical variables, whereas RT based on rate of perceived effort presented lower effect in the Timed Up and Go test. Although multimodal training is an effective intervention to increase physical capacity, caution should be taken regarding the period and the method to control RT intensity to optimize enhancements in frail older people.

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Critical illness myopathy in intensive care setting

QJM ◽

10.1093/qjmed/hcab086.044 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mostafa K Fouad ◽

Ashraf M Hazem ◽

Kareem M Elnaghy

Keyword(s):

Critical Illness ◽

Mortality Rate ◽

Usual Care ◽

Usual Care Group ◽

Fixed Effects ◽

Meta Analysis ◽

Care Group ◽

Fixed Effects Model ◽

Analysis Study ◽

Number Of Patients

Abstract Aim of the Work to provide cumulative data about the efficacy and safety of neuro-muscular electrical stimulation (NMES) combined with usual care (UC) versus usual care alone in ICU patients with Critical Illness Myopathy (CIM). Methodology The current systematic review was done on studies published between 2009 and 2019. The total number of patients in all the included studies was 1259 patients; 652 in NMES group, and 607 in UC group. Our data were divided into two groups: NMES (652 patients), and UC (607 patients). Metaanalysis study was done on 11 studies which described and compared the 2 different techniques for treatment of CIM; with overall number of patients (N = 1259). Results Regarding 1ry outcome measures, we found 8 studies reported critical Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and the overlap, critical care setting MRC scale for muscle strength, with total number of patients (N = 968). The random-effects model of the meta-analysis study showed non-significant difference in mean MRC scale in NMES group compared to usual care group (p > 0.05). We also found 11 studies reported ICU stay with total number of patients (N = 1259). The random-effects model of the meta-analysis study showed nonsignificant difference in mean ICU stay in NMES group compared to usual care group (p > 0.05). We also found only 2 studies reported SF-36 scale for quality of life, with total number of patients (N = 270). The fixed-effects model of the metaanalysis study showed highly significant decrease in mean SF-36 scale in NMES group compared to usual care group (p = 0.003). Regarding 2ry outcome measure, we found 3 studies reported CIM incidence with total number of patients (N = 394). The fixed-effects model of the meta-analysis study showed marked decrease in CIM incidence in NMES group compared to usual care group, but not reaching statistical significance (p > 0.05). We also found 9 studies reported mortality rate with total number of patients (N = 1044). The fixed-effects model of the meta-analysis study showed non-significant difference in mortality rate in NMES group compared to usual care. Our systematic review and meta-analysis showed that NMES combined with usual care was not associated with significant differences in global muscle strength, ICU stay, quality of life score, CIM incidence and mortality rate in comparison with usual care alone in critically ill patients. Conclusion NMES is not superior to usual care in management of CIM. Usual care remains the mainstay of management of CIM with significant better outcomes, in addition to preventive measures as early aggressive treatment of sepsis and MOF, blood glucose control, optimizing certain drugs use, early enteral nutrition, maintaining water, electrolyte and acidbase balance.

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Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data

BMJ Open ◽

10.1136/bmjopen-2020-040931 ◽

2020 ◽

Vol 10 (12) ◽

pp. e040931

Author(s):

Djillali Annane ◽

Romain Pirracchio ◽

Laurent Billot ◽

Andre Waschka ◽

Sylvie Chevret ◽

...

Keyword(s):

Septic Shock ◽

Usual Care ◽

Latin American ◽

Low Dose ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Primary Analysis ◽

Mixed Effect ◽

Meta Analyses

IntroductionThe benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock.Methods and analysisTo assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90 days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial.Ethics and disseminationThis IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access.PROSPERO registration numberCRD42017062198.

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Biological versus non-biological dressings in the management of split-thickness skin-graft donor sites: a systematic review and meta-analysis

Journal of Wound Care ◽

10.12968/jowc.2020.29.10.604 ◽

2020 ◽

Vol 29 (10) ◽

pp. 604-610

Author(s):

Shafiq Rahman ◽

Benjamin Langridge ◽

Ahmed Al-Hadad ◽

Rehman Ali Khan ◽

Muhammad Hyder Junejo ◽

...

Keyword(s):

Systematic Review ◽

Wound Healing ◽

Skin Graft ◽

Meta Analysis ◽

Healing Time ◽

Conclusive Evidence ◽

Split Thickness Skin Graft ◽

Controlled Trials ◽

Cochrane Central Register ◽

Thickness Skin

Objective: There are currently no definitive guidelines regarding the management of split-thickness skin-graft (STSG) donor sites. The literature reports biological and non-biological dressings as the two main groups; however, there is no conclusive evidence regarding the ideal type. A systematic review and meta-analysis of existing clinical trials was performed to compare biological and non-biological dressings in managing STSG donor sites. Method: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards was used to conduct this study. Electronic databases including MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched by two authors (SR and BL). Data analysis was performed with RevMan 5.3. Results: In total, 10 studies, consisting of eight randomised controlled trials and two observational assessments, were identified. Wound healing time was faster with biological dressings compared to non-biological dressings (mean difference -5.44 days; p<0.05). A higher epithelialisation rate was also noted for biological dressings. There was no difference in the infection rate between the two study groups (odds ratio [OR] 0.39; 95% confidence interval [CI] 0.15–1.04) or wound exudation (OR 0.31; 95% CI 0.01–8.28). The pain level experienced during dressing changes in both groups was reported to be similar. Conclusion: The rate of epithelialisation and wound healing is greater for STSG donor sites when treated with biological dressings, but they offer no difference in terms of reducing pain, limiting infection or exudation.

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Effect of pretreatment with midazolam on etomidate-induced myoclonus: A meta-analysis

Journal of International Medical Research ◽

10.1177/0300060516682882 ◽

2017 ◽

Vol 45 (2) ◽

pp. 399-406 ◽

Cited By ~ 3

Author(s):

Chengmao Zhou ◽

Yu Zhu ◽

Zhen Liu ◽

Lin Ruan

Keyword(s):

Incidence Rate ◽

Fixed Effects ◽

Meta Analysis ◽

Group Versus ◽

Cochrane Library ◽

Controlled Trials ◽

Fixed Effects Model ◽

Control Groups ◽

Randomized Controlled ◽

Review Manager

Objective To investigate the effect of pretreatment with midazolam on myoclonus induced by etomidate injection. Methods A meta-analysis was performed using Review Manager software, version 5.2. Two researchers independently searched PubMed, Cochrane Library, and Embase® databases for randomized controlled trials involving patients who underwent etomidate induced general anaesthesia with or without midazolam pretreatment, published between 1990 and 2016. Outcome measures comprised overall myoclonus incidence rate and incidence rate classified by degree of myoclonus following etomidate injection. Data were assessed using a fixed effects model. Results Five studies, comprising 302 patients, were included for analysis. Overall incidence rate of etomidate injection-induced myoclonus was significantly lower in the pooled midazolam group versus controls (relative risk [RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree of myoclonus showed significantly lower incidence in midazolam groups versus control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI 0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced myoclonus, and alleviate the degree of etomidate-induced myoclonus.

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Electroacupuncture for Gastrointestinal Function Recovery after Gynecological Surgery: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8329366 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Xiang Gao ◽

Yuzhuo Zhang ◽

Yizhe Zhang ◽

YuTzu Ku ◽

Yi Guo

Keyword(s):

Large Scale ◽

Ph Value ◽

Meta Analysis ◽

Control Group ◽

Controlled Trials ◽

Gastrointestinal Function ◽

Cochrane Central Register ◽

Gynecological Surgery ◽

Function Recovery ◽

Significant Difference

Background. Evidence for the efficacy and safety of electroacupuncture (EA) on gastrointestinal function recovery after gynecological surgery is unclear. Objective. This meta-analysis aimed to evaluate the effects of EA on recovery of postoperative gastrointestinal function for patients receiving gynecological surgery. Data sources: PubMed, Cochrane Central Register of Controlled Trials (CINAHL), Embase, China National Knowledge Infrastructure (CNKI), Weipu (CQVIP), and Wanfang databases were systematically searched from the inception dates to May 30, 2020, for relevant randomized controlled trials (RCTs). Study selection: RCTs that evaluated EA for postoperative gastrointestinal function directly related to gynecological surgery in adults aged 18 years or over. Data extraction and synthesis: paired reviewer independently extracted the data and assessed study quality. Standardized mean differences (SMD) were calculated as the effect measure from a random effects model. Main outcomes and measures: time to first flatus (TFF), time to bowel sounds recovery (TBS), and time to first defecation (TFD) were recorded as primary outcomes; postoperative nausea and vomiting (PONV), motilin (MTL), gastrin (GAS), pH value of gastric mucosa (pHi), gastric mucosal partial pressure of carbon dioxide (PgCO2), vasoactive intestinal peptide (VIP), and adverse event were reported as secondary outcomes. Results. We included eighteen RCTs (1117 participants). Our findings suggested that compared to the control group (CG), electroacupuncture group (EG) showed significant effects on TFF (SMD = −0.98, 95% CI: [−1.28, −0.68], P < 0.00001 , I2 = 69%), TBS (SMD = −0.98, 95% CI: [−1.84, −0.12], P = 0.03 , I2 = 92%), and TFD (SMD = −1.23, 95% CI: [−1.59, −0.88], P < 0.0001 , I2 = 0%). Moreover, the incidence of PONV at postoperative 6 h (OR = 0.42, 95% CI: [0.27, 0.64], P < 0.0001 , I2 = 0%) and 24 h (OR = 0.46, 95% CI: [0.32, 0.68], P < 0.0001 , I2 = 0%) was lower in the EG than that in the CG, whereas no significant difference in ratio of PONV at postoperative 48 h (OR = 0.55, 95% CI: [0.20, 1.51], P = 0.25 , I2 = 0%) was detected between the two groups. Meanwhile, there was a significant effect in favor of EA on the level of MTL at postoperative 6 h (SMD = −0.93, 95% CI: [−1.36, −0.61], P < 0.0001 , I2 = 21%), while no significant effect was observed at postoperative 24 h (SMD = −0.43, 95% CI: [−0.89, 0.02], P = 0.06 , I2 = 69%) in the EG when compared to the CG. Additionally, a large significant effect on decreasing PgCO2 was found in the EG in comparison to the CG, but no significant effect in favor of EA on GAS, VIP, or pHi was observed. It was reported that there was one participant with pain at the needling sites and bruising, and three participants withdrew because they were not intolerant to EA. Conclusions. EA could be a promising strategy for the prevention and treatment of gastrointestinal dysfunction after gynecological surgery, including shortening TFF and TFD, TBS, regulating MTL, and decreasing the ratio of PONV within postoperative 24h. The effects on MTL and PONV varied with different intervention points, and EA used at 30 min prior to surgery might be recommended. However, the evidence quality ranged from low to very low, and large-scale and high-quality RCTs were warranted.

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Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

10.1101/2020.09.30.20204693 ◽

2020 ◽

Author(s):

Joseph A. Ladapo ◽

John E. McKinnon ◽

Peter A. McCullough ◽

Harvey Risch

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Side Effects ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Randomized Controlled ◽

Exposure Prophylaxis

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

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