Probiotics for Preventing Ventilator-Associated Pneumonia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Background

Ventilator-associated pneumonia (VAP) is considered to be a worldwide issue along with the development of supportive ventilation. The preventing strategy is of great importance for its poor prognostic and difficulties in treatment. Probiotics have been advocated as one of the possible preventive measures. We conducted a systematic review and meta-analysis to explore the potential benefits of probiotics.

Methods

The databases, Web of science, PubMed, Ovid and Cochrane lib were searched for randomized controlled trials (RCTs) publications that compared the effectiveness of probiotics with placebo in the prevention of VAP. The incidence of VAP was considered as the primary endpoint, mortality, length of stay in intensive care units (ICUs), etiology of the infections were considered as secondary endpoints.

Results

A total of 844 patients from 5 trials were subjected to meta-analysis. Probiotics did not significantly decrease the incidence of VAP (RR 0.94, 95%CI 0.85-1.04, p=0.22), however, the administration of probiotics reduced the risk of VAP caused by Pseudomonas aeruginosa (P. aeruginosa) (RR 0.30, 95%CI 0.11-0.91, P=0.03). It failed to affect any other endpoints.

Conclusion

Probiotic prophylaxis of ventilator-associated pneumonia remained inconclusive and it failed to improve the prognosis of general mechanically ventilated patients. It was noteworthy that infections caused by P. aeruginosa was reduced by administration of probiotics. In further, it is recommended that advanced studies should exploit transformation in pathogenic microorganisms owing to administration of probiotics as well as the specific population.     

Effects of Exercise Modalities on Arterial Stiffness and Wave Reflection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants'' or exercise characteristics.

Methods

We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years.

Results

Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx.

Conclusions

We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline.

Trial Registration PROSPERO

Database registration: CRD42014009744,.     

Acupuncture Therapy for Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ObjectiveAcupuncture has commonly been used in China, either alone or in combination with Western medicine, to treat sudden sensorineural hearing loss (SSHL). The purpose of this systematic review is to assess the efficacy and safety of acupuncture therapy for patients with SSHL.MethodsWe searched PubMed, the Cochrane Library, Embase, China National Knowledge Internet (CNKI), Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical literature service system (SinoMed) to collect randomized controlled trials of acupuncture for SSHL published before July 2014. A meta-analysis was conducted according to the Cochrane systematic review method using RevMan 5.2 software. The evidence level for each outcome was assessed using the GRADE methodology.ResultsTwelve trials involving 863 patients were included. A meta-analysis showed that the effect of manual acupuncture combined with Western medicine comprehensive treatment (WMCT) was better than WMCT alone (RR 1.33, 95%CI 1.19–1.49) and the same as the effect of electroacupuncture combined with WMCT (RR 1.33, 95%CI 1.19–1.50). One study showed a better effect of electroacupuncture than of WMCT (RR 1.34, 95%CI 1.24–1.45). For mean changes in hearing over all frequencies, the meta-analysis showed a better effect with the combination of acupuncture and WMCT than with WMCT alone (MD 10.85, 95%CI 6.84–14.86). However, the evidence levels for these interventions were low or very low due to a high risk of bias and small sample sizes in the included studies.ConclusionThere was not sufficient evidence showing that acupuncture therapy alone was beneficial for treating SSHL. However, interventions combining acupuncture with WMCT had more efficacious results in the treatment of SSHL than WMCT alone. Electroacupuncture alone might be a viable alternative treatment besides WMCT for SSHL. However, given that there were fewer eligible RCTs and limitations in the included trials, such as methodological drawbacks and small sample sizes, large-scale RCTs are required to confirm the current findings regarding acupuncture therapy for SSHL.     

Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Low levels of 25-OH vitamin D are associated with respiratory tract infection (RTI). However, results from randomized controlled trials are inconclusive. Therefore, we performed a systematic review and meta-analysis to assess the preventive effect of vitamin D supplementation on RTI.

Methods

Randomized, controlled trials of vitamin D for prevention of RTI were used for the analysis. The risks of within-trial and publication bias were assessed. Odds ratios of RTI were pooled using a random-effects model. Heterogeneity was assessed using Cochran''s Q and I². Meta-regressions and subgroup analyses were used to assess the influence of various factors on trial outcome. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013003530.

Findings

Of 1137 citations retrieved, 11 placebo-controlled studies of 5660 patients were included in the meta-analysis. Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cohran''s Q p<0.0001, I² = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias.

Interpretation

Results indicate that vitamin D has a protective effect against RTI, and dosing once-daily seems most effective. Due to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution.     

Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment.

Objective

To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment.

Methods

We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies'' web sites electronically up to Dec 30^th, 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates.

Results

We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin.

Conclusions

Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment.     

Acute Endovascular Reperfusion Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Randomized controlled trials (RCTs) of endovascular therapy for acute ischemic stroke have had inconsistent results. We evaluated the efficacy and safety of endovascular therapy in published RCTs.

Methods

We performed a systematic review of RCTs of endovascular therapy with thrombolytic or mechanical reperfusion compared with interventions without endovascular therapy. Primary outcome was the frequency of good functional outcome (modified Rankin scale (mRS) of 0-2 at 90 days) and secondary outcomes were mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analysis was performed and the Cochrane risk of bias assessment was used to evaluate quality of evidence.

Results

Ten studies involving 1,612 subjects were included. Endovascular therapy was not significantly associated with good functional outcome (Relative Risk [RR] =1.17; 95% CI, 0.97 to 1.42; p=0.10 and Absolute Risk Difference [ARD] =7%; 95%CI -0.1% to 14%; p=0.05); heterogeneity was moderate among studies (I²=30%). Mortality was unchanged with endovascular therapy (RR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in sICH (RR=1.20; 95 % CI, 0.79 to 1.82; p=0.39). The quality of evidence was low for all outcomes and the recommendation is weak for the use of endovascular therapy as per GRADE methodology.

Conclusions

Intra-arterial therapy did not show significant increase in good outcomes and no changes in either mortality or sICH in patients with acute ischemic stroke. We need further RCTs with better design and quality to evaluate the true efficacy of endovascular therapy.     

Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review

ObjectivesTo quantify the proportion of randomized controlled trials (RCTs) specifically designed for elderly, and to assess their characteristics, as compared to RCTs not specifically designed for elderly.DesignReview and synthesis of published literature.MeasurementsWe searched PubMed for articles published in the year 2012. We included RCTs. Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported. A random sample of 10% was drawn and of this selection the following trial characteristics were extracted: sample size, disease category, age of sample, and age-related inclusion criteria. Clinical trials were defined to be specifically designed for elderly if a lower age cut-off of ≥ 55 years was used, or when participants had an average age of ≥ 70 years.ResultsThe search strategy yielded 26,740 articles, from which a random sample was drawn, resulting in 2375 articles. After exclusion, data was extracted from 1369 publications. Of these 1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with trials not designed for older adults, trials designed for elderly contained a significantly larger median number of participants (125 vs. 80, p = 0.008) significantly more trials designed for elderly fell into the disease categories eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and circulatory system (16% vs. 9%, p = 0.039). No significant difference was observed with regard to the other disease categories.ConclusionThere is a low proportion of RCTs specifically designed for elderly. As older patients will increasingly form the majority in medical practice, there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults.     

Suvorexant for Primary Insomnia: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Objective

We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.

Methods

Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations through June 27, 2015. We performed a systematic review and meta-analysis of suvorexant trial efficacy and safety outcomes. The primary efficacy outcomes were either subjective total sleep time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary outcomes were other efficacy outcomes, discontinuation rate, and individual adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean difference (WMD) and 95% confidence intervals (CI) based on a random effects model were calculated.

Results

The computerized literature database search initially yielded 48 results, from which 37 articles were excluded following a review of titles and abstracts and another eight review articles after full-text review. Thus, we identified 4 trials that included a total of 3,076 patients. Suvorexant was superior to placebo with regard to the two primary efficacy outcomes (sTST: WMD = −20.16, 95% CI = −25.01 to −15.30, 1889 patients, 3 trials, sTSO: WMD = −7.62, 95% CI = −11.03 to −4.21, 1889 patients, 3 trials) and was not different from placebo in trial discontinuations. Suvorexant caused a higher incidence than placebo of at least one side effects, abnormal dreams, somnolence, excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.

Conclusions

Our analysis of published trial results suggests that suvorexant is effective in treating primary insomnia and is well-tolerated.     

Effectiveness of Pulsed Electromagnetic Fields on Bone Healing: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The effect of pulsed electromagnetic field (PEMF) on bone healing is still uncertain and it has not been established as a standardized treatment. The aim of this systematic review and meta-analysis is to evaluate the effect of PEMF on bone healing in patients with fracture. We searched CNKI, Wan Fang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database, and Open Grey websites for randomized controlled trials (published before July 2019 in English or Chinese) comparing any form of PEMF to sham. Reference lists were also searched. Related data were extracted by two investigators independently. The bias risk of the articles and the evidence strength of the outcomes were evaluated. Twenty-two studies were eligible and included in our analysis (n = 1,468 participants). The pooled results of 14 studies (n = 1,131 participants) demonstrated that healing rate in PEMF group was 79.7% (443/556), and that in the control group was 64.3% (370/575). PEMF increased healing rate (RR = 1.22; 95% confidence interval [CI] = 1.10–1.35; I² = 48%) by the Mantel–Haenszel analysis, relieved pain (standardized mean difference (SMD) = −0.49; 95% CI = −0.88 to −0.10; I² = 60%) by the inverse variance analysis, and accelerated healing time (SMD = −1.01; 95% CI = −2.01 to −0.00; I² = 90%) by the inverse variance analysis. Moderate quality evidence suggested that PEMF increased healing rate and relieved pain of fracture, and very low-quality evidence showed that PEMF accelerated healing time. Larger and higher quality randomized controlled trials and pre-clinical studies of optimal frequency, amplitude, and duration parameters are needed. © 2020 Bioelectromagnetics Society.     

Acetyl-L-Carnitine in the Treatment of Peripheral Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

Acetyl-L-carnitine (ALC), a constructive molecule in fatty acid metabolism, is an agent potentially effective for treating peripheral neuropathic pain (PNP). Its effect, however, remains uncertain. We aimed to access the efficacy and safety of ALC for the treatment of patients with PNP.

Methods

We searched MEDLINE (1996–2014), EMBase (1974–2014), and CENTRAL (May 2014) up to June 27, 2014 for randomized controlled trials (RCTs) comparing ALC with placebo or other active medications in diabetic and non-diabetic PNP patients that reported the change of pain using visual analogue scale (VAS). Mean difference (MD) and 95% confidence interval (CI) were used for pooling continuous data.

Results

Four RCTs comparing ALC with placebo and reporting in three articles (n = 523) were included. Compared with placebo, ALC significantly reduced VAS scores of PNP patients (MD of VAS, 1.20; 95% CI, 0.68-1.72, P <0.00001). In the subgroup analysis, the effect of ALC on VAS was similar in different administration routes (intramuscular-oral sequential subgroup: MD, 1.19; 95% CI, 0.34-2.04, P = 0.006; oral only subgroup: pooled MD, 1.15; 95%CI, 0.33-1.96, P = 0.006), and ALC appeared more effective in diabetic PNP patients than non-diabetic PNP patients (diabetic subgroup: MD, 1.47; 95%CI, 1.06-1.87, P <0.00001; non-diabetic subgroup: MD, 0.71; 95% CI, -0.01-1.43, P = 0.05). No severe adverse events were reported related to ALC. The common adverse events were pain, headache, paraesthesia, hyperesthesia, retching, biliary colic, and gastrointestinal disorders. The rates of total adverse events were similar in ALC and control group.

Conclusion

The current evidence suggests that ALC has a moderate effect in reducing pain measured on VAS in PNP patients with acceptable safety. Larger trials with longer follow-up, however, are warranted to establish the effects.     

Taurolidine Lock Solutions for the Prevention of Catheter-Related Bloodstream Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Catheter-related bloodstream infections (CRBSIs) are a significant cause of morbidity and mortality in critically ill patients, contributing to prolonged hospital stays and increased costs. Whether taurolidine lock solutions (TLS) are beneficial for the prevention of CRBSIs remains controversial. In this meta-analysis, we aim to assess the efficacy of TLS for preventing CRBSIs.

Methods

We conducted a systematic search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials that reported on the effects of TLS for preventing CRBSIs. The primary outcome in these studies was catheter-related bloodstream infections, with microbial distribution of CRBSI and catheter-associated thrombosis as secondary outcomes. Data were combined using random-effects models owing to significant clinical heterogeneity.

Results

Six randomized controlled trials (RCTs) conducted from 2004 through 2013 involving 431 patients and 86,078 catheter-days were included in the review. TLS were significantly associated with a lower incidence of CRBSIs when compared to heparin lock solutions (Risk Ratio [RR], 0.34; 95% Confidence Interval [CI], 0.21–0.55). Use of TLS significantly decreased the incidence of CRBSIs from gram-negative (G−) bacteria (P = 0.004; RR, 0.27; CI, 0.11–0.65), and was associated with a non-significant decrease in gram-positive (G+) bacterial infections (P = 0.07; RR, 0.41; CI, 0.15–1.09). No significant association was observed with TLS and catheter-associated thrombosis (RR, 1.99; CI, 0.75–5.28).

Conclusions

The use of TLS reduced the incidence of CRBSIs without obvious adverse effects or bacterial resistance. However, the susceptibility of G+ and G- bacteria to taurolidine and the risk for catheter-associated thrombosis of TLS are indeterminate due to limited data. The results should be treated with caution due to the limited sample sizes and methodological deficiencies of included studies. Therefore, additional well-designed and adequately powered RCTs are needed to confirm these findings.     

The Effect of Black Tea on Blood Pressure: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Objective

Epidemiological evidence has linked consumption of black tea, produced from Camellia sinensis, with a reduced risk of cardiovascular diseases. However, intervention studies on the effects of tea consumption on blood pressure (BP) have reported inconsistent results. Our objective was to conduct a systematic literature review with meta-analysis of controlled human intervention studies examining the effect of tea consumption on BP.

Methods

We systematically searched Medline, Biosis, Chemical Abstracts and EMBASE databases through July 2013. For inclusion, studies had to meet the following pre-defined criteria: 1) placebo controlled design in human adults, 2) minimum of 1 week black tea consumption as the sole intervention, 3) reported effects on systolic BP (SBP) or diastolic BP (DBP) or both. A random effects model was used to calculate the pooled overall effect of black tea on BP.

Results

Eleven studies (12 intervention arms, 378 subjects, dose of 4–5 cups of tea) met our inclusion criteria. The pooled mean effect of regular tea ingestion was −1.8 mmHg (95% CI: −2.8, −0.7; P = 0.0013) for SBP and −1.3 mmHg (95% CI: −1.8, −0.8; P<0.0001) for DBP. In covariate analyses, we found that the method of tea preparation (tea extract powders versus leaf tea), baseline SBP and DBP, and the quality score of the study affected the effect size of the tea intervention (all P<0.05). No evidence of publication bias could be detected.

Conclusions

Our meta-analysis indicates that regular consumption of black tea can reduce BP. Although the effect is small, such effects could be important for cardiovascular health at population level.     

The Influence of Anti-Infective Periodontal Treatment on C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Periodontal infections are hypothesized to increase the risk of adverse systemic outcomes through inflammatory mechanisms. The magnitude of effect, if any, of anti-infective periodontal treatment on systemic inflammation is unknown, as are the patient populations most likely to benefit. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to test the hypothesis that anti-infective periodontal treatment reduces systemic c-reactive protein (CRP).

Methods and Findings

MEDLINE, EMBASE, CENTRAL and CINAHL databases were searched using sensitivity-enhancing search terms. Eligible RCTs enrolled patients with periodontal infection, compared a clearly defined anti-infective periodontal intervention (experimental group) to an “inactive control” (no periodontal intervention) or to an “active control” (lower treatment intensity than the experimental group). Mean differences in final CRP values at the earliest post-treatment time point (typically 1-3 months) between experimental and control groups were analyzed using random-effects regression. Among 2,753 possible studies 20 were selected, which included 2,561 randomized patients(median=57). Baseline CRP values were >3.0 mg/L in 40% of trials. Among studies with a control group receiving no treatment, the mean difference in CRP final values among experimental treatment vs. control groups was -0.37 mg/L [95%CI=-0.64, -0.11], (P=0.005), favoring experimental treatment. Trials for which the experimental group received antibiotics had stronger effects (P for interaction=0.03) and the mean difference in CRP final values among experimental treatment vs. control was -0.75 mg/L [95%CI=-1.17,-0.33]. No treatment effect was observed among studies using an active treatment comparator. Treatment effects were stronger for studies that included patients with co-morbidities vs. studies that included “systemically healthy” patients, although the interaction was not significant (P=0.48).

Conclusions

Anti-infective periodontal treatment results in short-term modest reductions in systemic CRP.     

The Effects of Perioperative Music Interventions in Pediatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

Music interventions are widely used, but have not yet gained a place in guidelines for pediatric surgery or pediatric anesthesia. In this systematic review and meta-analysis we examined the effects of music interventions on pain, anxiety and distress in children undergoing invasive surgery.

Data Sources

We searched 25 electronic databases from their first available date until October 2014.

Study Selection

Included were all randomized controlled trials with a parallel group, crossover or cluster design that included pediatric patients from 1 month to 18 years old undergoing minimally invasive or invasive surgical procedures, and receiving either live music therapy or recorded music.

Data Extraction and Synthesis

4846 records were retrieved from the searches, 26 full text reports were evaluated and data was extracted by two independent investigators.

Main Outcome Measures

Pain was measured with the Visual Analogue Scale, the Coloured Analogue Scale and the Facial Pain Scale. Anxiety and distress were measured with an emotional index scale (not validated), the Spielberger short State Trait Anxiety Inventory and a Facial Affective Scale.

Results

Three RCTs were eligible for inclusion encompassing 196 orthopedic, cardiac and day surgery patients (age of 1 day to 18 years) receiving either live music therapy or recorded music. Overall a statistically significant positive effect was demonstrated on postoperative pain (SMD -1.07; 95%CI-2.08; -0.07) and on anxiety and distress (SMD -0.34 95% CI -0.66; -0.01 and SMD -0.50; 95% CI -0.84; - 0.16.

Conclusions and Relevance

This systematic review and meta-analysis indicates that music interventions may have a statistically significant effect in reducing post-operative pain, anxiety and distress in children undergoing a surgical procedure. Evidence from this review and other reviews suggests music therapy may be considered for clinical use.     

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes.

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews.

Eligibility Criteria for Selecting Studies

Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions.

Results

Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02).

Conclusions

This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.     

Early versus Delayed Antiretroviral Therapy for HIV and Tuberculosis Co-Infected Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ObjectiveTo compare important clinical outcomes between early and delayed initiation of antiretroviral therapy (ART) in adults who had a co-infection of human immunodeficiency virus (HIV) and tuberculosis (TB).MethodsWe performed a systematic search for relevant publications on PubMed, EMBASE, and the International Clinical Trials Registry Platform. We included randomized controlled trials (RCTs) that compared early ART initiation (within four weeks after anti-TB treatment starting) and delayed ART initiation (after eight weeks but less than twelve weeks of anti-TB treatment starting) in the course of TB treatment. Pooled estimates with corresponding 95% confidence interval (95%CI) were calculated with random-effects model. Sensitivity analysis was performed to investigate the stability of pooled estimates.ResultsA meta-analysis was evaluated from six RCTs with 2272 participants. Compared to delayed ART initiation, early ART initiation significantly reduces all-cause mortality in HIV-positive patients with TB [incidence rate ratio (IRR) 0.75, 95%CI 0.59 to 0.95; I² = 0.00%; p = 0.67], even though there is an increased risk for IRD [IRR 2.29, 95%CI 1.81 to 2.91; I²2 = 0.00%; p = 0.56]. Additionally, early ART initiation was not associated with an increased risk for grade 3-4 drug-related adverse events [IRR 0.99, 95%CI 0.83 to 1.18; I² = 0.00%; p = 0.56].ConclusionsAlthough limited evidence, our results provide support for early ART initiation in the course of anti-TB treatment. However, more well-designed cohort or intervention studies are required to further confirm our findings.