Validity of Qualis database as a predictor of evidence hierarchy and risk of bias in randomized controlled trials: a case study in dentistry

OBJECTIVE:

To evaluate the validity of the Qualis database in identifying the levels of scientific evidence and the quality of randomized controlled trials indexed in the Lilacs database.

METHODS:

We selected 40 open‐access journals and performed a page‐by‐page hand search, to identify published articles according to the type of study during a period of six years. Classification of studies was performed by independent reviewers assessed for their reliability. Randomized controlled trials were identified for separate evaluation of risk of bias using four dimensions: generation of allocation sequence, allocation concealment, blinding, and incomplete outcome data. The Qualis classification was considered to be the outcome variable. The statistical tests used included Kappa, Spearman''s correlation, Kendall‐tau and ordinal regressions.

RESULTS:

Studies with low levels of scientific evidence received similar Qualis classifications when compared to studies with high levels of evidence. In addition, randomized controlled trials with a high risk of bias for the generation of allocation sequences and allocation concealment were more likely to be published in journals with higher Qualis levels.

DISCUSSION:

The hierarchy level of the scientific evidence as classified by type of research design, as well as by the validity of studies according to the bias control level, was not correlated or associated with Qualis stratification.

CONCLUSION:

Qualis classifications for journals are not an approximate or indirect predictor of the validity of randomized controlled trials published in these journals and are therefore not a legitimate or appropriate indicator of the validity of randomized controlled trials.     

Randomized trial - oxybutynin for treatment of persistent plantar hyperhidrosis in women after sympathectomy

OBJECTIVE:

Hyperhidrosis is a common disease, and thoracoscopic sympathectomy improves its symptoms in up to 95% of cases. Unfortunately, after surgery, plantar hyperhidrosis may remain in 50% of patients, and compensatory sweating may be observed in 70%. This clinical scenario remains a challenge. Our objective was to evaluate the effectiveness of oxybutynin in the treatment of persistent plantar hyperhidrosis and compensatory sweating and its effects on quality of life in women after thoracoscopic sympathectomy.

METHOD:

We conducted a prospective, randomized study to compare the effects of oxybutynin at 10 mg daily and placebo in women with persistent plantar hyperhidrosis. The assessment was performed using a quality-of-life questionnaire for hyperhidrosis and sweating measurement with a device for quantifying transepidermal water loss. Clinicaltrials.gov: NCT01328015.

RESULTS:

Sixteen patients were included in each group (placebo and oxybutynin). There were no significant differences between the groups prior to treatment. After oxybutynin treatment, there was a decrease in symptoms and clinical improvement based on the quality-of-life questionnaire (before treatment, 40.4 vs. after treatment, 17.5; p = 0.001). The placebo group showed modest improvement (p = 0.09). The outcomes of the transepidermal water loss measurements in the placebo group showed no differences (p = 0.95), whereas the oxybutynin group revealed a significant decrease (p = 0.001). The most common side effect was dry mouth (100% in the oxybutynin group vs. 43.8% in the placebo group; p = 0.001).

CONCLUSION:

Oxybutynin was effective in the treatment of persistent plantar hyperhidrosis, resulting in a better quality of life in women who had undergone thoracoscopic sympathectomy.     

The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis

Study Objectives:

To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder.

Design:

Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990–2009).

Patients:

Individuals with delayed sleep phase disorder.

Interventions:

Administration of melatonin.

Measurements and Results:

A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89–1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45–0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 –41.72 min). The wake-up time and total sleep time did not change significantly.

Conclusions:

Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder.

Citation:

van Geijlswijk IM; Korzilius HPLM; Smits MG. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. SLEEP 2010;33(12):1605-1614.     

Twenty Months of Evolution Following Sympathectomy on Patients with Palmar Hyperhidrosis: Sympathectomy at the T3 Level is Better than at the T2 Level

OBJECTIVE

To compare two surgical techniques (denervation levels) for sympathectomy using video-assisted thoracoscopy to treat palmar hyperhidrosis in the long-term.

METHODS

From May 2003 to June 2006, 60 patients with palmar hyperhidrosis were prospectively randomized for video-assisted thoracoscopic sympathectomy at the T2 or T3 ganglion level. They were followed for a mean of 20 months and were evaluated regarding their degree of improvement of palmar hyperhidrosis, incidence and severity of compensatory hyperhidrosis and its evolution over time, and quality of life.

RESULTS

Fifty-nine cases presented resolution of the palmar hyperhidrosis. One case of therapeutic failure occurred in the T3 group. Most of the patients presented an improvement in palmar hyperhidrosis, without any difference between the groups. Twenty months later, all patients in both groups presented some degree of compensatory hyperhidrosis but with less severity in the T3 group (p = 0.007). Compensatory hyperhidrosis developed in most patients during the first month after the operation, with incidence and severity that remained stable over time. An improvement in quality of life was seen starting from the first postoperative evaluation but without any difference between the groups. This improvement was maintained until the end of the follow-up.

CONCLUSION

Both techniques were effective for treating palmar hyperhidrosis. The most frequent complication was compensatory hyperhidrosis, which presented stable incidence and severity over the study period. Sympathectomy at the T3 level presented compensatory hyperhidrosis with less severity. Nevertheless, the improvement in quality of life was similar between the groups.     

Differences between the real and the desired worlds in the results of clinical trials

OBJECTIVE:

We refer to the effectiveness (known as pragmatic or real world) and efficacy (known as explanatory or desired or ideal world) of interventions. However, these terms seem to be randomly chosen by investigators who design clinical trials and do not always reflect the true purpose of the study. A pragmatic-explanatory continuum indicator summary tool was thus developed with the aim of identifying the characteristics of clinical trials that distinguish between effectiveness and efficacy issues. We verified whether clinical trials used the criteria proposed by the indicator summary tool, and we categorized these clinical trials according to a new classification.

METHOD:

A systematic survey of randomized clinical trials was performed. We added a score ranging from 0 (more efficacious) to 10 (more effective) to each domain of the indicator summary tool and proposed the following classifications: high efficacy (<25), moderate efficacy (25-50), moderate effectiveness (51-75), and high effectiveness (<75).

RESULTS:

A total of 844 randomized trials were analyzed. No analyzed trials used the criteria proposed by the indicator summary tool. Approximately 44% of the trials were classified as having moderate effectiveness, and 43.82% were classified as having moderate efficacy.

CONCLUSIONS:

Most clinical trials used the term “efficacy” to illustrate the application of results in clinical practice, but the majority of those were classified as having moderate effectiveness according to our proposed score. The classification based on the 0-100 score is still highly subjective and can be easily misunderstood in all domains based on each investigator''s own experiences and knowledge.     

Effect of atorvastatin in patients with chronic heart failure – insights from randomized clinical trials

Introduction

Recent large clinical trials have yielded disappointing results of rosuvastatin in the chronic heart failure (CHF) population. The question that remains is whether these results of rosuvastatin studies could be extended to other statins. Therefore, we performed a meta-analysis based on all currently available randomized controlled trials (RCTs) to evaluate the clinical efficacy of atorvastatin in CHF patients.

Material and methods

The published literature was scanned by formal searches of electronic databases up to January 2010. RCTs were eligible for inclusion if they compared atorvastatin versus placebo treatment in patients with CHF and reported the clinical outcomes.

Results

Pre-specified criteria were met by 7 trials involving 540 patients. The primary endpoint, all-cause mortality, was significantly reduced with atorvastatin therapy compared with placebo in CHF patients (odds ratio [OR] 0.39, P = 0.002), with similar results in cardiovascular mortality (OR 0.28, P = 0.002) and sudden cardiac death (OR 0.24, P = 0.01). There was also a significant decrease in hospitalization for worsening CHF with atorvastatin therapy compared with placebo (OR 0.30, P < 0.001).

Conclusions

This meta-analysis suggests the effectiveness of atorvastatin treatment in reducing the risks of all-cause mortality and worsening CHF hospitalization in patients with CHF. Further large, well-conducted randomized trials are needed to confirm the benefits of atorvastatin or other statins for CHF relative to placebo or rosuvastatin.     

Arch height and maximum rearfoot eversion during jogging in 2 static neutral positions

Context:

Clinically, lowering of the medial longitudinal arch is believed to be closely related to rearfoot eversion. However, the relationship between arch height and rearfoot eversion during gait is unclear.

Objectives:

(1) To examine the influence of 2 reference positions (weight-bearing neutral position [WBNP] and subtalar neutral position [STNP]) on maximum rearfoot eversion, tibial internal rotation, knee flexion, knee internal rotation, and dorsiflexion-plantar flexion of ankle joint measures during jogging and (2) to compare the relationships among static arch height, navicular drop, and the 2 maximum rearfoot eversion measures.

Design:

Crossover study.

Setting:

Gait laboratory.

Patients or Other Participants:

Thirty-three volunteers between 18 and 40 years of age.

Intervention(s):

Each participant stood on the treadmill in 2 static positions: WBNP and STNP. Kinematic data were obtained using a 10-camera motion analysis system (120 Hz) when participants jogged at 2.65 m/s on the treadmill in bare feet.

Main Outcome Measure(s):

Rearfoot and shank angular kinematics, navicular drop, and static arch height.

Results:

Maximum rearfoot eversion was greater (WBNP: 4.03° ± 2.58°, STNP: 10.91° ± 5.34°) when STNP was the static reference (P < .001). A strong correlation was seen between maximum STNP eversion and navicular drop (r = 0.842) but not between WBNP and navicular drop (r = 0.216). Differences were noted in dorsiflexion and knee kinematics during gait between the static references; however, the effect sizes were low, and the mean differences were smaller than 2°, which was less than 5% of total excursion during gait.

Conclusions:

Using STNP rather than WBNP as the reference position affects estimates of frontal-plane rearfoot movement but not other ankle or knee motions in jogging.     

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES:

Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment.

METHOD:

A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients'' outcomes were analyzed. ClinicalTrials.gov: NCT00979290.

RESULTS:

A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up.

CONCLUSIONS:

In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.     

Objective evaluation of plantar hyperhidrosis after sympathectomy

OBJECTIVE:

The aim of the present study was to prospectively, randomly, blindly, and objectively investigate how surgery affects plantar sudoresis in patients with palmar and plantar hyperhidrosis over a one-year period using a sudorometer (VapoMeter).

METHODS:

From February 2007 to May 2009, 40 consecutive patients with combined palmar hyperhidrosis and plantar hyperhidrosis underwent video-assisted thoracic sympathectomy at the T3 or T4 ganglion level (15 women and 25 men, with a mean age of 25 years).

RESULTS:

Immediately after the operation and during the one-year follow-up, all of the patients were free from palmar hyperhidrosis episodes. Compensatory hyperhidrosis of varying degrees was observed in 35 (87.5%) patients after one year. Only two (2.5%) patients suffered from severe compensatory hyperhidrosis. There was a large initial improvement in plantar hyperhidrosis in 46.25% of the cases, followed by a progressive regression of that improvement, such that only 30% continued to show this improvement after one year. The proportion of patients whose condition worsened increased progressively (from 21.25% to 47.50%), and the proportion of stable patients decreased (32.5% to 22.50%). This was not related to resection level; however, a lower intensity of plantar hyperhidrosis prior to sympathectomy correlated with worse evolution.

CONCLUSION:

Patients with palmar hyperhidrosis and plantar hyperhidrosis who underwent video-assisted thoracic sympathectomy to treat their palmar hyperhidrosis exhibited good initial improvement in plantar hyperhidrosis, which then decreased to lesser degrees of improvement over a one-year period following the surgery. For this reason, video-assisted thoracic sympathectomy should not be performed when only plantar hyperhidrosis is present.     

Tumor necrosis factor-α antibodies (infliximab,adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis

Introduction

This meta-analysis compares the effectiveness and safety of tumor necrosis factor α (TNF-α) antibodies (infliximab, adalimumab and certolizumab) with either a placebo or each of them in the treatment of Crohn''s disease (CD).

Material and methods

A systematic review of literature published up to November 2012 was performed and a meta-analysis of identified studies was carried out. We searched the following databases: PubMed, EMBASE, The Cochrane Library and others. Only randomized or clinical controlled trials were included.

Results

Nineteen clinical trials fulfilled the established criteria (5 studies for infliximab vs. placebo, 6 for each adalimumab or certolizumab vs. placebo and 2 comparing infliximab with adalimumab). The results of meta-analysis showed that anti-TNF therapy in patients with CD is safe and statistically significantly more effective when compared with the placebo for induction of remission at week 4 (RB = 1.90, 95% CI: 1.55–2.33, p < 0.00001), maintenance of remission at weeks 20–30 (RB = 1.86, 95% CI: 1.61–2.15, p < 0.00001) and at weeks 48–56 (RB = 2.75, 95% CI: 2.13–3.54, p < 0.00001) in patients who responded to the induction therapy and patients randomized before the induction. Anti-TNF agents were also superior to the placebo in fistula healing (during short-term induction, as well as long-term maintenance) and inducing CR-70 but not CR-100 at week 4. Moreover, the anti-TNF therapy had a significant effect on achieving both CR-70 and CR-100 during long-term maintenance.

Conclusions

Infliximab, adalimumab and certolizumab are effective as both induction and maintenance therapy in moderate to severe Crohn''s disease in adults, including patients with fistulas. The safety profile was acceptable.     

Meta-analysis of randomized trials on access site selection for percutaneous coronary intervention in ST-segment elevation myocardial infarction

Introduction

Superior outcomes with transradial (TRPCI) versus transfemoral coronary intervention (TFPCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI) have been suggested by earlier studies. However, this effect was not evident in randomized controlled trials (RCTs), suggesting a possible allocation bias in observational studies. Since important studies with heterogeneous results regarding mortality have been published recently, we aimed to perform an updated review and meta-analysis on the safety and efficacy of TRPCI compared to TFPCI in the setting of STEMI.

Material and methods

Electronic databases were searched for relevant studies from January 1993 to November 2012. Outcome parameters of RCTs were pooled with the DerSimonian-Laird random-effects model.

Results

Twelve RCTs involving 5,124 patients were identified. According to the pooled analysis, TRPCI was associated with a significant reduction in major bleeding (odds ratio (OR): 0.52 (95% confidence interval (CI) 0.38–0.71, p < 0.0001)). The risk of mortality and major adverse events was significantly lower after TRPCI (OR = 0.58 (95% CI: 0.43–0.79), p = 0.0005 and OR = 0.67 (95% CI: 0.52–0.86), p = 0.002 respectively).

Conclusions

Robust data from randomized clinical studies indicate that TRPCI reduces both ischemic and bleeding complications in STEMI. These findings support the preferential use of radial access for primary PCI.     

Local anesthesia with epinephrine is safe and effective for oral surgery in patients with type 2 diabetes mellitus and coronary disease: a prospective randomized study

OBJECTIVE:

To investigate the variations in blood glucose levels, hemodynamic effects and patient anxiety scores during tooth extraction in patients with type 2 diabetes mellitus T2DM and coronary disease under local anesthesia with 2% lidocaine with or without epinephrine.

STUDY DESIGN:

This is a prospective randomized study of 70 patients with T2DM with coronary disease who underwent oral surgery. The study was double blind with respect to the glycemia measurements. Blood glucose levels were continuously monitored for 24 hours using the MiniMed Continuous Glucose Monitoring System. Patients were randomized into two groups: 35 patients received 5.4 mL of 2% lidocaine, and 35 patients received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Hemodynamic parameters (blood pressure and heart rate) and anxiety levels were also evaluated.

RESULTS:

There was no difference in blood glucose levels between the groups at each time point evaluated. Surprisingly, both groups demonstrated a significant decrease in blood glucose levels over time. The groups showed no significant differences in hemodynamic and anxiety status parameters.

CONCLUSION:

The administration of 5.4 mL of 2% lidocaine with epinephrine neither caused hyperglycemia nor had any significant impact on hemodynamic or anxiety parameters. However, lower blood glucose levels were observed. This is the first report using continuous blood glucose monitoring to show the benefits and lack of side effects of local anesthesia with epinephrine in patients with type 2 diabetes mellitus and coronary disease.     

Adherence in Internet Interventions for Anxiety and Depression: Systematic Review

Background

Open access websites which deliver cognitive and behavioral interventions for anxiety and depression are characterised by poor adherence. We need to understand more about adherence in order to maximize the impact of Internet-based interventions on the disease burden associated with common mental disorders.

Objective

The aims of this paper are to review briefly the adherence literature with respect to Internet interventions and to investigate the rates of dropout and compliance in randomized controlled trials of anxiety and depression Web studies.

Methods

A systematic review of randomized controlled trials using Internet interventions for anxiety and depression was conducted, and data was collected on dropout and adherence, predictors of adherence, and reasons for dropout.

Results

Relative to reported rates of dropout from open access sites, the present study found that the rates of attrition in randomized controlled trials were lower, ranging from approximately 1 - 50%. Predictors of adherence included disease severity, treatment length, and chronicity. Very few studies formally examined reasons for dropout, and most studies failed to use appropriate statistical techniques to analyze missing data.

Conclusions

Dropout rates from randomized controlled trials of Web interventions are low relative to dropout from open access websites. The development of theoretical models of adherence is as important in the area of Internet intervention research as it is in the behavioral health literature. Disease-based factors in anxiety and depression need further investigation.     

Medial tibial stress syndrome: evidence-based prevention

Reference:

Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32–40.

Clinical Question:

Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates?

Data Sources:

Studies were identified by searching MEDLINE (1966–2000), Current Contents (1996–2000), Biomedical Collection (1993–1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted.

Study Selection:

Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS.

Data Extraction:

A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors'' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers'' scores.

Main Results:

Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods.

Conclusions:

No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury.     

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES:

Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis.

METHODS:

Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers).

RESULTS:

An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found.

CONCLUSION:

An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.     

Implementation of pay for performance in primary care: a qualitative study 8 years after introduction

Background

Pay for performance is now a widely adopted quality improvement initiative in health care. One of the largest schemes in primary care internationally is the English Quality and Outcomes Framework (QOF).

Aim

To obtain a longer term perspective on the implementation of the QOF.

Design and setting

Qualitative study with 47 health professionals in 23 practices across England.

Method

Semi-structured interviews.

Results

Pay for performance is accepted as a routine part of primary care in England, with previous more individualistic and less structured ways of working seen as poor practice. The size of the QOF and the evidence-based nature of the indicators are regarded as key to its success. However, pay for performance may have had a negative impact on some aspects of medical professionalism, such as clinical autonomy, and led a significant minority of GPs to prioritise their own pay rather than patients’ best interests. A small minority of GPs tried to increase their clinical autonomy with further unintended consequences.

Conclusion

Pay for performance indicators are now welcomed by primary healthcare teams and GPs across generations. Almost all interviewees wanted to see a greater emphasis on involving front line practice teams in developing indicators. However, almost all GPs and practice managers described a sense of decreased clinical autonomy and loss of professionalism. Calibrating the appropriate level of clinical autonomy is critical if pay for performance schemes are to have maximal impact on patient care.     

Interpreting the outcomes of automated internet-based randomized trials: example of an International Smoking Cessation Study

Background

Smoking is one of the largest contributors to the global burden of disease. Internet interventions have been shown to reduce smoking rates successfully. However, improved methods of evaluating effectiveness need to be developed for large-scale Internet intervention trials.

Objective

To illustrate a method to interpret outcomes of large-scale, fully automated, worldwide Internet intervention trials.

Methods

A fully automated, international, Internet-based smoking cessation randomized controlled trial was conducted in Spanish and English, with 16,430 smokers from 165 countries. The randomized controlled trial replicated a published efficacy trial in which, to reduce follow-up attrition, 1000 smokers were followed up by phone if they did not provide online follow-up data.

Results

The 7-day self-reported abstinence rates ranged from 36.18% (2239/6189) at 1 month to 41.34% (1361/3292) at 12 months based on observed data. Given high rates of attrition in this fully automated trial, when participants unreachable at follow-up were presumed to be smoking, the abstinence rates ranged from 13.63% (2239/16.430) at 1 month to 8.28% (1361/16,430) at 12 months. We address the problem of interpreting results with high follow-up attrition rates and propose a solution based on a smaller study with intensive phone follow-up.

Conclusions

Internet-based smoking cessation interventions can help large numbers of smokers quit. Large-scale international outcome studies can be successfully implemented using automated Internet sites. Interpretation of the studies’ results can be aided by extrapolating from results obtained from subsamples that are followed up by phone or similar cohort maintenance methods.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00721786","term_id":"NCT00721786"}}NCT00721786; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00721786","term_id":"NCT00721786"}}NCT00721786 (Archived by WebCite at http://www.webcitation.org/63mhoXYPw)     

The impact of tracheotomy on levels of procalcitonin in patients without sepsis: a prospective study

OBJECTIVE:

Procalcitonin is a reliable biomarker of infection and sepsis. We aimed to determine whether tracheotomy influences the procalcitonin concentrations in patients without sepsis and assess whether operative duration and procedure affect the peak procalcitonin level.

METHODS:

A total of 38 non-septic patients who required a tracheotomy underwent either a percutaneous dilatational tracheotomy (n=19) or a surgical tracheotomy (n=19). Procalcitonin levels were measured at the beginning of the tracheotomy and at 2 h, 4 h, 8 h, 24 h, 48 h and 72 h after the procedure.

RESULTS:

The baseline procalcitonin concentration before the tracheotomy was 0.24±0.13 ng/mL. The postoperative levels increased rapidly, with a 4-fold elevation after 2 h, reaching a peak 4 h later with a 5-fold increase over baseline. Thereafter, the levels gradually returned to 2-fold greater than the baseline level within 72 h. The peak levels of procalcitonin showed a significant positive correlation with operative durations (r=0.710, p<0.001) and procedures (rho=0.670, p<0.001).

CONCLUSION:

In patients without sepsis, tracheotomy induces a rapid release of serum procalcitonin, and the operative duration and procedure have significant impacts on the peak procalcitonin levels. Thus, the nonspecific increase in procalcitonin levels following tracheotomy needs to be considered when this measure is used to evaluate infection.     

Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

Introduction:

Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.

Methodology:

We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.

Results:

A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I² =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I² = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I² = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I² = 0%).

Conclusion:

The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.