High-quality Randomized Clinical Trials Research Articles

Prevention of diaper dermatitis in infants--a literature review.

Diaper dermatitis (DD) is one of the most common skin conditions in neonates and infants, with a peak between the ages of 9 and 12months. Appropriate skin care practices that support skin barrier function and protect the buttocks skin from urine and feces are supposed to be effective in the prevention of DD. Despite many recommendations for parents and caregivers on proper diaper skin care, there is no up-to-date synthesis of the available evidence to develop recommendations for DD prevention practice. Therefore we performed a systematic literature review on the efficacy of nonmedical skin care practices on the diapered area of healthy, full-term infants ages 0 to 24months. We identified 13 studies covering skin care practices such as cleansing, bathing, and application of topical products. DD prevalence and incidence and physiologic skin parameters were used as efficacy parameters. The results of this review indicate that cleansing of the diaper area using baby wipes or water and a washcloth have comparable effects on diapered skin. Bathing with a liquid baby cleanser twice weekly seems comparable with water alone. The application of ointments containing zinc oxide or petrolatum with or without vitamin A seems to have comparable effects on DD severity. There seems to be no information on whether single skin care practices such as cleansing, bathing, and application of topical preparations can prevent DD. High-quality randomized clinical trials are needed to show the effectiveness of skin care practices for controlling and preventing DD.

Randomized Controlled Trials in the Journal of Sexual Medicine: A Quality Assessment and Relevant Clinical Impact

Quality assessment of randomized clinical trials (RCTs) is important to prevent the adoption of findings of low-quality trials into clinical practice. The aim if this study was to analyze the quality of studies reporting RCTs in the Journal of Sexual Medicine (JSM) and to find relevant clinical impact. A quality assessment was conducted in all studies identified as RCTs published in the JSM from 2004 to 2012. The review period was divided into three periods: early (2004-2006), mid (2007-2009), and late (2010-2012). The Jadad scale, van Tulder scale, and the Cochrane Collaboration Risk of Bias Tool (CCRBT) quality scoring instruments were used. The RCTs were also categorized by country of origin, topic, the inclusion of institutional review board (IRB) approval, funding, citation rate, and impact factor. A total of 2,418 original articles were published in the JSM during the review period, and 188 were reports of RCTs. There were 39 (14.89%), 70 (7.77%), and 76 (6.29%) RCTs published during the early, mid, and late terms, respectively (P < 0.001). No significant increases in Jadad or van Tulder scale scores were found over time nor were there any significant changes in the number of low-risk articles as assessed by the CCRBT. However, significant differences in quality analysis were found in funding and IRB approval. Citation rates and impact factor were not correlated with RCT quality using any of the tools. The number of original articles and RCTs published in the JSM increased over time. However, the ratio of RCTs to original articles did not increase significantly. Adequate randomization and blinding methods, IRB review, and financial support are required for the conduct of high-quality RCTs.

Safety and efficacy of early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis

BackgroundTirofiban has been widely used as an adjunctive pharmacologic agent for revascularization in patients undergoing percutaneous coronary intervention, and the outcomes appear attractive. However, the potential benefits from early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remain unclear.MethodsWe conducted a search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to September 2012 without language restriction. A total of eight randomized trials (n=1 577 patients) comparing early (emergency department or ambulance) versus late (catheterization laboratory) administration of tirofiban in STEMI patients undergoing PPCI were included in this meta-analysis. Risk ratio (RR) was computed from individual studies and pooled with random- or fixed-effect models.ResultsThere were no differences in post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and Corrected TIMI Frame Count (RR=1.02, 95% confidence interval (CI): 0.99–1.05,P=0.18; weighted mean difference (WMD)=-0.93, 95%CI: -5.37–3.52,P=0.68, respectively) between the two groups. Similarly, there were no significant differences in the incidence of 30-day mortality (RR=1.69, 95%CI: 0.69–4.13,P=0.25) and re-myocardial infarction (RR=0.71, 95%CI: 0.21–2.35,P=0.57) between early and late administration of tirofiban. As to the safety end points, no significant difference was observed in hospital minor bleeding (RR=1.08, 95%CI: 0.54–2.14,P=0.83) and hospital and 30-day major bleeding between the two groups (RR=0.98, 95%CI: 0.46–2.10,P=0.96;RR=1.32, 95%CI: 0.59–2.97,P=0.49, respectively).ConclusionsEarly administration of tirofiban in patients undergoing PPCI for STEMI was safe, but no beneficial effects on post-procedural angiographic or clinical outcomes could be identified as compared with late administration. Besides the negative finding, more high-quality randomized clinical trials are still needed to explore the efficacy of adequate, earlier administration of tirofiban in patients undergoing PPCI.

Vitamin D as add-on therapy for multiple sclerosis

Vitamin D as add-on therapy for multiple sclerosis

Reply to Dr Grzybowski

Sir, We thank Dr Grzybowski for his interest in our manuscript. His comments1 are consistent with those that we mentioned in the paper: ‘a significant increase in the antibiotic resistance of the isolated specimens from ocular flora' and ‘a greater rate of endophthalmitis with the use of topical antibiotics'.2 As we stated in our manuscript, we reviewed the articles that have been published in the literature from January 2005 to November 2012.2 After our manuscript was in press, several reports, including those discussed by Dr Grzybowski, were published describing the use of antibiotics in intravitreal injections. Although high-quality prospective randomized clinical trials comparing the rate of post-injection endophthalmitis have not been conducted, there is a growing body of evidence that shows that the routine use of antibiotics before or after intravitreal injections should be discouraged.3, 4, 5 It is noteworthy that the use of pre- and/or post-injection antibiotics may still be considered in selected conditions such as eyes with external ocular diseases, nasolacrimal drainage problems, or history of endophthalmitis, as well as monocular patients. Once again we thank Dr Grzybowski for his comments, which have allowed us the opportunity to respond.

Meta-analysis of acupuncture for relieving non-organic dyspeptic symptoms suggestive of diabetic gastroparesis

BackgroundAcupuncture is widely used to treat diabetic patients with dyspeptic symptoms suggestive of gastroparesis in China. We conducted this systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for diabetic gastroparesis (DGP).MethodsWe searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese databases including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM) and WanFang Data up to January 2013 without language restriction. Eligible RCTs were designed to examine the efficacy of acupuncture in improving dyspeptic symptoms and gastric emptying in DGP. Risk of bias, study design and outcomes were extracted from trials. Relative risk (RR) was calculated for dichotomous data. Mean difference (MD) and standardized mean difference (SMD) were selected for continuous data to pool the overall effect.ResultsWe searched 744 studies, among which 14 RCTs were considered eligible. Overall, acupuncture treatment had a higher response rate than controls (RR, 1.20 [95% confidence interval (CI), 1.12 to 1.29], P < 0.00001), and significantly improved dyspeptic symptoms compared with the control group. There was no difference in solid gastric emptying between acupuncture and control. Acupuncture improved single dyspeptic symptom such as nausea and vomiting, loss of appetite and stomach fullness. However, most studies were in unclear and high risk of bias and with small sample size (median = 62). The majority of the RCTs reported positive effect of acupuncture in improving dyspeptic symptoms.ConclusionsThe results suggested that acupuncture might be effective to improve dyspeptic symptoms in DGP, while a definite conclusion about whether acupuncture was effective for DGP could not be drawn due to the low quality of trials and possibility of publication bias. Further large-scale, high-quality randomized clinical trials are needed to validate this claim and translate this result to clinical practice.

Management of Asymptomatic Internal Carotid Artery Stenosis

Optimal management of patients with asymptomatic carotid artery stenosis remains unclear. Although 2 high-quality randomized clinical trials demonstrated reductions in ispsilateral stroke rates in patients without symptoms after carotid endarterectomy, medical therapy of asymptomatic carotid artery stenosis has reduced rates of stroke to approximately 1% per year, raising questions about the generalizability of these previous trials to current medical practice. However, reductions in adverse events after revascularization can make revascularization more attractive. The emergence of percutaneous revascularization for carotid artery stenosis has raised further questions about optimal management of asymptomatic carotid artery stenosis. This Grand Rounds summarizes the factors to consider when counseling patients and making clinical decisions regarding medical therapy and revascularization for patients with asymptomatic carotid artery stenosis. This information should provide clinicians with the knowledge base to counsel patients about the risks and benefits of treatment options.

Efficacy of Short‐Term High‐Dose Atorvastatin Pretreatment in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta‐analysis of Nine Randomized Controlled Trials

The efficacy of short-term high-dose atorvastatin pretreatment in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) remains unclear. This meta-analysis was undertaken to assess the efficacy of short-term high-dose atorvastatin pretreatment in patients with ACS undergoing PCI. Short-term high-dose atorvastatin pretreatment may be beneficial in reducing major adverse cardiac events (MACEs) and improving myocardial blood flow in patients with ACS undergoing PCI. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically reviewed for randomized controlled trials (RCTs) published up to March 2013, in which short-term high-dose atorvastatin pretreatment was compared with control for patients with ACS undergoing PCI. The primary outcome measure was the incidence of MACEs at 30 days. The meta-analysis was performed with the fixed effect model or random-effects model according to the heterogeneity. Meta-analysis was performed by RevMan 5.0 software (Cochrane Collaboration, Copenhagen, Denmark). Nine RCTs incorporating 952 patients met the inclusion criteria and were included in this meta-analysis. Short-term high-dose atorvastatin pretreatment significantly reduced the incidence of MACEs at 30-day follow-up (risk ratio [RR] 0.39, 95% confidence interval [Cl]: 0.25 to 0.61, P < 0.001) and improved the final Thrombolysis in Myocardial Infarction (TIMI) flow grade (RR 1.08, 95% Cl: 1.02 to 1.14, P = 0.01) compared with controls. There were no significant differences in peak creatine kinase-myocardial band and high-sensitivity C-reactive protein level post-PCI between the 2 groups, though there were favorable trends related to statin use. As to the safety end points, no significant difference was observed in elevated liver aminotransferase level between short-term high-dose atorvastatin pretreatment and control groups (RR 1.36, 95% Cl: 0.67 to 2.74). The use of short-term high-dose atorvastatin pretreatment is safe and significantly improves the final TIMI flow grade as well as reduces the 30-day MACEs in ACS patients post-PCI. This finding encourages the use of short-term high-dose atorvastatin pretreatment as an alternative for ACS patients undergoing PCI, but more high-quality randomized clinical trials are still needed to confirm the long-term efficacy and safety.

AB0375 Efficacy and safety of non-biologic immunusuppresants in the treatment of non-renal systemic lupus erythematosus: a systematic review

BackgroundTo date, few randomised clinical trials (RCTs) have analyzed the effect of the available therapies on non-renal manifestations of SLE. Specifically, there is limited evidence on the efficacy of non-biologic...

Adjunctive photodynamic therapy to non‐surgical treatment of chronic periodontitis: a systematic review and meta‐analysis

To investigate the efficacy of antimicrobial photodynamic therapy (aPDT) adjunctive to scaling root planing (SRP) in patients with chronic periodontitis. A meta-analysis was conducted according to the PRISMA statement and Cochrane Collaboration recommendations. Two independent reviewers performed an extensive literature search and manual search on seven databases. Mean differences (MD) and 95% confidence intervals (CI) were calculated for clinical attachment level (CAL) gain and probing depth (PD) reduction. The I(2) test was used for inter-study heterogeneity. Publication bias was examined by Egger's regression test and the trim-and-fill method. Sensitivity analysis of 14 randomized clinical trials (RCTs) revealed differences in PD reduction (MD 0.19, 95% CI 0.07-0.31, p=0.002) and CAL gain (MD 0.37, 95% CI 0.26-0.47, p<0.0001) in favour of SRP+aPDT, with no evidence of heterogeneity. Subgroup analysis revealed the absence of heterogeneity in RCTs, with high risk of bias for PD reduction and CAL gain. No evidence of publication bias was detected. The use of adjunctive aPDT to conventional SRP provides short-term benefits. The evidence to support its clinical medium/long-term efficacy is insufficient. Further high-quality RCTs are needed to investigate the influence of potential confounders on the efficacy of adjunctive aPDT.

Prevention of venous thromboembolism in patients undergoing surgical treatment of varicose veins

There is no consensus among surgeons with regard to prevention of venous thromboembolism (VTE) in patients undergoing surgical treatment of varicose veins. We performed a systematic review of the available literature. We systematically searched the online database from PubMed for studies about the incidence of VTE and thromboprophylaxis in varicose vein surgery. We included 13 papers for review. The incidence of VTE after varicose vein surgery remains unclear. Most retrospective case series report an incidence of deep venous thrombosis (DVT) of approximately 1%, based on a clinical diagnosis. However, three prospective studies have systematically detected DVT by means of duplex ultrasound and showed that the true incidence might be 5-10 times higher than expected on a clinical basis. Discussion More data on the incidence of VTE, and the need for postoperative thromboprophylaxis are necessary to formulate evidence-based clinical guidelines. Therefore, high-quality randomised clinical trials, with high numbers of included patients, and ideally comparing prophylaxis to placebo are warranted.

Mandibular Manipulation for the Treatment of Temporomandibular Disorder

The aim of this study was to conduct a systematic review to identify the randomized clinical studies that had investigated the following research question: Is the mandibular manipulation technique an effective and safe technique for the treatment of the temporomandibular joint disk displacement without reduction? The systematic search was conducted in the electronic databases: PubMed (Medical Publications), LILACS (Latin American and Caribbean Literature in Health Sciences), EMBASE (Excerpta Medica Database), PEDro (Physiotherapy Evidence Database), BBO (Brazilian Library of Odontology), CENTRAL (Library Cochrane), and SciELO (Scientific Electronic Library Online). The abstracts of presentations in physical therapy meetings were manually selected, and the articles of the ones that meet the requirements were investigated. No language restrictions were considered. Only randomized and controlled clinical studies were included. Two studies of medium quality fulfilled all the inclusion criteria. There is no sufficient evidence to support the effectiveness of the mandibular manipulation therapy, and therefore its use remains questionable. Being minimally invasive, this therapy is attractive as an initial approach, especially considering the cost of the alternative approaches. The analysis of the results suggests that additional high-quality randomized clinical trials are necessary on the topic, and they should focus on methods for data randomization and allocation, on clearly defined outcomes, on a priori calculated sample size, and on an adequate follow-up strategy.

Primary Prevention of Atrial Fibrillation - The Path Untread.

The prevalence and incidence of atrial fibrillation (AF) is on the rapid rise. To slow down the AF epidemic, effective primary prevention strategies need to be instituted. Unfortunately, this is an area that has not been well-explored. There is a multitude of risk factors that predispose to the development of AF. Of these, the most common from an epidemiologic perspective are advanced age, hypertension, diabetes, ischemic heart disease, and heart failure. The first-line pharmacologic therapies for these predisposing conditions (e.g. beta blockers, renin-angiotensin system inhibitors, statins, and omega-3 fatty acids) appear to also have potential roles in the primary prevention of AF. Definitive data, however, is lacking as to efficacy of these drugs for this particular purpose. Large-scale, high-quality randomized clinical trials on AF primary preventive strategies are urgently required in order to guide clinical practice. For now, adherence to the guideline-based therapies of each individual risk factor appears to be the most reasonable approach for the primary prevention of AF.

Effect of statins on chronic inflammation and nutrition status in renal dialysis patients: A systematic review and meta‐analysis

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may have an adjunctive effect on chronic inflammation and nutrition status in renal dialysis patients. Therefore, we performed a systematic review of randomized controlled trials to assess the effect of statins on chronic inflammation and nutrition status in dialysis patients. The randomized controlled trials (RCTs) of statins versus placebo or no treatment for renal dialysis patients were searched from PubMed, EMbase and Cochran Central Register of Controlled Trials. We screened relevant studies according to predefined inclusion and exclusion criteria, evaluated the quality of the included studies, and performed meta-analyses by using the Cochrane Collaboration's Revman 5.1 software. We identified nine trials including 3098 patients. Meta-analysis showed statins can significantly decrease the serum C-reactive protein (CRP) (SMD, -0.54; 95% confidence interval (CI), -1.04 to -0.05; P = 0.03) and high sensitivity CRP (hs-CRP) level (SMD, -0.72; 95% CI, -1.14 to -0.31; P = 0.0007) of dialysis patients compared with that of the control group. However, statins did not differ significantly from the control group in increasing the serum Alb level (SMD, -0.13; 95% CI, -0.42 to 0.15; P = 0.37). Statins can improve the chronic inflammation status reflected by the decreasing of serum CRP and hs-CRP levels, whereas there is no conclusive evidence that it can improve the nutrition status. However, this result needs to be further confirmed in more high-quality randomized clinical trials.

Systematic reviews showed insufficient evidence for clinical practice in 2004: what about in 2011? The next appeal for the evidence‐based medicine age

The aims of the Cochrane systematic reviews are to make readily available and up-to-date information for clinical practice, offering consistent evidence and straightforward recommendations. In 2004, we evaluated the conclusions from Cochrane systematic reviews of randomized controlled trials in terms of their recommendations for clinical practice and found that 47.83% of them had insufficient evidence for use in clinical practice. We proposed to reanalyze the reviews to evaluate whether this percentage had significantly decreased. A cross-sectional study of systematic reviews published in the Cochrane Library (Issue 7, 2011) was conducted. We randomly selected reviews across all 52 Cochrane Collaborative Review Groups. We analyzed 1128 completed systematic reviews. Of these, 45.30% concluded that the interventions studied were likely to be beneficial, of which only 2.04% recommended no further research. In total, 45.04% of the reviews reported that the evidence did not support either benefit or harm, of which 0.8% did not recommend further studies and 44.24% recommended additional studies; the latter has decreased from our previous study with a difference of 3.59%. Only a small number of the Cochrane collaboration's systematic reviews support clinical interventions with no need for additional research. A larger number of high-quality randomized clinical trials are necessary to change the 'insufficient evidence' scenario for clinical practice illustrated by the Cochrane database. It is recommended that we should produce higher-quality primary studies in active collaboration and consultation with global scholars and societies so that this can represent a major component of methodological advance in this context.

Meta‐analysis: nonsteroidal anti‐inflammatory drugs in biliary colic

Biliary colic is a common manifestation of cholelithiasis, developing in about one-third of patients. Even if nonsteroid anti-inflammatory drugs (NSAIDs) have widely been used to relieve biliary pain, there is a lack of systematic review of treatments on this issue. To assess the potential benefits in terms of both pain control and reduction of complications, and the potential harms of NSAIDs in patients with biliary colic. Data from randomised clinical trials (RCTs) comparing NSAIDs with no treatment, placebo or other drugs in patients with biliary colic, were collected from Medline and Embase. The outcome measures were expressed as odds ratio and relative risk and then pooled using fixed or random-effect models. Eleven RCTs involving 1076 subjects (268 men, 808 women; 18-86 years), including 442 controls were analysed. In comparison with placebo, NSAIDs led to a significantly higher proportion of patients with complete pain relief (RR 3.77, 95%CI 1.65-8.61; I(2) : 73%) and a significantly lower rate of complications (RR 0.53, 95% CI 0.31-0.89; I(2) : 35%). In comparison with other drugs, NSAIDs were more efficacious in controlling pain than spasmolytics (RR 1.47, 95% CI 1.03-2.10; I(2) : 55%); there was no difference between NSAIDs and opioids (RR 1.05, 95% CI 0.82-1.33; I(2) : 74%). In patients with biliary colic NSAIDs are the first-choice treatments as they control pain with the same efficacy of opioids and significantly reduce the proportion of patients with severe complications. However, the lack of high-quality RCTs and the presence of consistent heterogeneity among studies may partially flaw these results.

Intraoperative mild hypothermia for postoperative neurological deficits in intracranial aneurysm patients.

Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage, which is one of the most devastating clinical conditions. Clinically, it can be classified into five grades using the Hunt-Hess or World Federation of Neurological Surgeons (WFNS) scale. Grades 4 and 5 predict poor prognosis and are called 'poor grade', while grade 1, 2, and 3 are known as 'good grade'. Disturbances of intracranial homeostasis and brain metabolism are known to play certain roles in the sequelae. Hypothermia has a long history of being used to reduce metabolism rate, thereby protecting organs in cases where metabolism is disturbed and potentially harmful. To assess the effect of intraoperative mild hypothermia on postoperative death and neurological deficits in patients with intracranial aneurysms (ruptured or unruptured). We searched the Cochrane Stroke Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1950 to September 2011), EMBASE (1980 to September 2011), Science Citation Index (1900 to September 2011) and 11 Chinese databases (September 2011). We also searched ongoing trials registers (September 2011) and scanned reference lists of retrieved records. We included only randomised controlled trials comparing intraoperative mild hypothermia (32°C to 35°C) with control (no hypothermia) in patients with intracranial aneurysms (ruptured or unruptured). Two review authors independently selected trials and assessed the risk of bias for each included study. We presented data as risk ratio (RR) with 95% confidence intervals (CI). We included three studies enrolling 1158 patients. Each study observed an increased rate of good recovery with intraoperative mild hypothermia, but the effect sizes were not sufficient for statistical significance. A total of 76 of 577 patients (13.1%) who received hypothermia and 93 of 581 patients (16.0%) who did not receive hypothermia were dead or dependent. A total of 1086 of the1158 patients (93.8%) had good-grade aneurysmal subarachnoid haemorrhage. A random-effects meta-analysis resulted in a summarised RR of 0.82 (95% CI 0.62 to 1.09, P value 0.17). In patients with poor-grade aneurysmal subarachnoid haemorrhage, one of seven in the hypothermia group and one of six in the control group were dead or dependent (RR 0.86, 95% CI 0.07 to 10.96, P value 0.91). In patients without subarachnoid haemorrhage, three of 30 patients (10%) in the hypothermia group, and four of 29 patients (13.8%) in the control group were dead or dependent (RR 0.72, 95% CI 0.18 to 2.96, P value 0.65). In patients with good-grade aneurysmal subarachnoid haemorrhage, intraoperative mild hypothermia might prevent death or dependency in activities of daily living for a few of them. However, the confidence intervals include the possibility of both benefit and harm. There is no evidence that intraoperative mild hypothermia is harmful. This treatment should not be routinely applied. In patients with poor-grade aneurysmal subarachnoid haemorrhage or without subarachnoid haemorrhage, there are insufficient data to draw any conclusions. A high-quality randomised clinical trial of intraoperative mild hypothermia for postoperative neurological deficits in patients with poor-grade aneurysmal subarachnoid haemorrhage might be feasible.

Evidence-based assessment of the efficacy and effectiveness of light/laser activation in in-office dental bleaching

Many in-office bleaching techniques use the light/laser in conjunction with the bleaching agent claiming more favorable bleaching results. Controversy still exists in the literature as to the role of a light/laser in bleaching results. The goal of this study is to determine, through Comparative Effectiveness-Efficacy Research and Analysis for Practice (CEERAP), if the co-use of light/laser activation with the chemical bleaching agent has improved teeth whitening compared to using the chemical bleaching agent alone. Systematic reviews and randomized clinical trials on the research question were obtained using multiple search engines. Assessment of the level and quality of evidence and acceptable sample analysis were performed for the Randomized Clinical Trials (RCTs). Due to heterogeneity of the acceptable studies, meta-analysis was performed only on the two most homogenous studies. Qualitative assessment of the acceptable studies was performed. The strength of clinical recommendation was assessed. Only one qualitative systematic review was found. Eight articles were accepted as high quality RCTs. The meta-analysis shows preferable outcome when using the light activation with the bleaching material than when using the bleaching material alone. Qualitative assessment of the acceptable studies shows conflicting results. Most studies agreed that the use of light is proven to increase the whitening effect of the bleaching agent, especially for a short term after treatment. Additional studies with greater consistency in methodology and outcomes are needed to be able to reach a definite consensus regarding the effectiveness of using light during bleaching through an overarching meta-analysis for more powerful statistical results.

Evaluation of Treatment Effectiveness for the Herniated Cervical Disc

Systematic review. To assess the effectiveness of interventions for treating cervical disc herniation. Cervical disc herniation is 1 of the 23 specific disorders included in the CANS (Complaints of the Arm, Neck, and/or Shoulder) model. Treatment options range from conservative to surgical, but evidence for the effectiveness of these interventions is not yet well documented. The Cochrane Library, MEDLINE, EMBASE, PEDro, and CINAHL were searched for relevant systematic reviews and randomized clinical trials (RCTs) up to February 2009. Two reviewers independently selected relevant studies, assessed the methodological quality, and extracted data. Pooling of the data was not possible; thus, a best-evidence synthesis was used to summarize the results. Of the 11 RCTs included, 1 compared conservative with surgical intervention, and 10 compared various surgical interventions. No evidence was found for the effectiveness of conservative treatment (nonsteroidal anti-inflammatory drugs, cortisonics, and physical therapy) compared with percutaneous nucleoplasty. Moderate evidence was found for the effectiveness of anterior cervical discectomy with fusion (ACDF) using a titanium cage compared with ACDF using polymethyl methacrylate, and for BRYAN cervical disc (Medtronic Sofamor Danek, Memphis, TN) prostheses compared with ACDF using allograft bone and plating. No outcomes regarding adjacent-level disease were reported. There is conflicting evidence for the effectiveness of ACD compared with ACDF. Only limited or no evidence was found for the other surgical interventions. No evidence for effectiveness of conservative treatment compared with surgery was found. Although there is moderate evidence for the effectiveness of some surgical interventions, no unequivocal evidence for the superiority of 1 particular surgical treatment was found. Worldwide, most patients receive supplementary implants; however, cervical discectomy without graft may be preferred because of similar outcomes, lower costs, and possibly a lower risk of adjacent-level disease. More high-quality RCTs using validated outcome measures (including adjacent level disease) are needed.

Role of the hospital pharmacy and therapeutics committee in detecting and regulating off-label drug use

Dear Sir, We have read the article published by Duran-Garcia et al. [1] and would like to congratulate the authors on their work. Moreover, based on our own experience, we would also like to highlight the importance of the role of the Pharmacy and Therapeutics Committee in detecting and regulating the ‘‘off-label’’ drug use in hospitals. Prescription-indication studies can be used to detect if medication is being used in ways other than those authorised by the drug regulatory agencies. This non-approved use is called ‘‘off-label’’ drug use [2]. Our work area focuses on cytostatic drugs, and we know that the ‘‘offlabel’’ use of these drugs become a common practice in some hospitals [3–5]. For example, Conde-Garcia M et al. [3] found that Rituximab was used to treat unauthorised diagnoses (18 diagnoses) in 37.1% of patients between 2003 and 2007. Additionally, Rituximab was used in unauthorised chemotherapy plans (use with other cytostatic drugs) and lines of treatment (order of preference for the treatment alternatives available) in a considerable number of cases. On the other hand, Vargas-Rivas et al. [4] found that Trastuzumab was used in patients (36.4% of cases) who did not have HER2-Overexpressing (HER2-Overexpressing is one of the requirements established by regulatory agencies for using this drug). When situations like these are detected, it is important to assess whether use of the medication is pertinent or suitable. To assess it, first it is necessary to search for scientific evidence supporting the use of drugs in these unauthorised conditions (‘‘off-label’’ use). If evidence is not found or may be of moderate/lowquality, new studies should be designed to evaluate the effectiveness of the ‘‘off-label’’ drug use, and, ideally, to evaluate the cost-effectiveness ratio of treatment. In the study by Conde-Garcia et al. [3], the off-label use of the CHOP-Rituximab plan to treat follicular lymphoma (48.1% of plans used in this diagnosis) was supported by the results of high-quality randomised clinical trials [6, 7]. As a result, the ‘‘off-label’’ use of CHOP-Rituximab during the study period was deemed reasonable. Moreover, this chemotherapy plan was later approved and authorised by the national drug regulatory agency. In other words, ‘‘offlabel’’ drug use could be sometimes the correct treatment approach and can have positive effects on patient health, even before this use is approved by regulatory boards. On these occasions, the work carried out by the hospital Pharmacy and Therapeutics Committee becomes particularly important, as one of its main objectives is to assess the suitability of the ‘‘off-label’’ drug use [1]. If high-quality scientific evidence supporting the ‘‘off-label’’ drug use is found, the committee can decide to authorise this use in the corresponding hospitals, accepting the entailed advantages and drawbacks. Furthermore, as we mentioned above, the evidence supporting the ‘‘off-label’’ drug use could be not found or may be of moderate/low-quality [3] (i.e. poor-quality randomised controlled trials and/or several phase II studies). This situation should be the starting point for well-designed studies, which could generate evidence for the benefit/risk ratio of treatments, and help us to decide whether the ‘‘offlabel’’ use of a certain drug could be suitable. In these studies, it is important to include a specialist physician in the research team. With this fact, we want to ensure that clinical outcomes are correctly assessed and interpreted, J. E. Vargas-Rivas (&) D. Sabater-Hernandez M. A. Calleja-Hernandez M. J. Faus F. Martinez-Martinez Pharm. D. Pharmaceutical Care Research Group, Grupo de Investigacion en Atencion Farmaceutica, University of Granada, Campus Universitario de Cartuja S/N, 18071 Granada, Spain e-mail: jevargasrivas@gmail.com