Bacterial protease alleviate chronic liver fibrosis induced by thioacetamide through suppression of hepatic stellate cells consequently decrease its proliferative index.

In chronic liver diseases, liver fibrosis occurs due to excessive extracellular matrix (ECM) protein accumulation. Approximately 2 million deaths occur yearly due to liver disease, while cirrhosis is the 11th most common cause of death. Therefore, newer compounds or biomolecules must be synthesized to treat chronic liver diseases. In this aspect, the present study focuses on the assessment of the anti-inflammatory and antioxidant impact of Bacterial Protease (BP) produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) and 4,4'-(2,5-dimethoxy-1,4-phenylene) bis (1-(3-ethoxy phenyl)-1H-1,2,3-triazole) (DPET) in the treatment of early stage of liver fibrosis induced by thioacetamide (TAA). Sixty male rats were divided into six groups, ten rats each as follows: (1) Control group, (2) BP group, (3) TAA group, (4) TAA-Silymarin (S) group, (5) TAA-BP group, and (6) TAA-DPET group. Liver fibrosis significantly elevated liver function ALT, AST, and ALP, as well as anti-inflammatory interleukin 6 (IL-6) and VEGF. The oxidative stress parameters (MDA, SOD, and NO) were significantly increased with a marked reduction in GSH. Expression of MAPK and MCP-1 was unregulated in the TAA group, with downregulation of Nrf2 was observed. TAA caused histopathological alterations associated with hepatic vacuolation and fibrosis, increasing collagen fibers and high immuno-expression of VEGF. On the other hand, treatment with BP successfully improved the severe effects of TAA on the liver and restored histological architecture. Our study concluded the protective potentials of BP for attenuating liver fibrosis and could be used as adjuvant therapy for treating hepatic fibrosis.

The Impact of Micro RNA-320a Serum Level on Severity of Symptoms and Cerebral Processing of Pain in Patients with Fibromyalgia.

OBJECTIVES: The aim of this work was to explore the expression of miR-320a level in fibromyalgia patients in comparison to healthy controls, and to clarify its impact on the severity of symptoms and the cerebral processing of pain assessed by middle latency somatosensory evoked potentials (SSEPs). DESIGN: Case-control study. SETTING: Rheumatology and Neurology outpatient clinics. SUBJECTS: Seventy-four fibromyalgia patients and seventy-four normal healthy controls. METHODS: The included patients were subjected to detailed history taking, assessment of severity of fibromyalgia symptoms using the Fibromyalgia Impact Questionnaire Revised (FIQR), assessment of pain intensity using the Neuropathic Pain Symptom Inventory (NPSI), measurement of the serum level of miR-320a in addition to of measurement peak latencies and amplitudes of middle latency SSEPs. RESULTS: Fibromyalgia patients had significantly higher micro-RNA-320a levels (0.907 ± 0.022) in comparison to controls (0.874 ± 0.015) (P-value < .001). The mean values of micro-RNA-320a levels were significantly higher in fibromyalgia patients with insomnia, chronic fatigue syndrome, persistent depressive disorder, and primary headache disorder than those without (P-value = .024, <.001, .006, .036 respectively). There were statistically significant positive correlations between micro-RNA-320a levels, and disease duration, FIQR, and NPSI total scores (P-value <0.001, 0.003, 0.002 respectively). There were no statistically significant correlations between micro-RNA-320a levels and middle latency SSEPs. DISCUSSION: Micro-RNA-320a level is significantly upregulated in fibromyalgia patient. It has a crucial impact on the severity of symptoms but not related to the cerebral processing of pain.

The Potential of Physical Exercise to Mitigate Radiation Damage-A Systematic Review.

There is a need to investigate new countermeasures against the detrimental effects of ionizing radiation as deep space exploration missions are on the horizon. Objective: In this systematic review, the effects of physical exercise upon ionizing radiation-induced damage were evaluated. Methods: Systematic searches were performed in Medline, Embase, Cochrane library, and the databases from space agencies. Of 2,798 publications that were screened, 22 studies contained relevant data that were further extracted and analyzed. Risk of bias of included studies was assessed. Due to the high level of heterogeneity, meta-analysis was not performed. Five outcome groups were assessed by calculating Hedges' g effect sizes and visualized using effect size plots. Results: Exercise decreased radiation-induced DNA damage, oxidative stress, and inflammation, while increasing antioxidant activity. Although the results were highly heterogeneous, there was evidence for a beneficial effect of exercise in cellular, clinical, and functional outcomes. Conclusions: Out of 72 outcomes, 68 showed a beneficial effect of physical training when exposed to ionizing radiation. As the first study to investigate a potential protective mechanism of physical exercise against radiation effects in a systematic review, the current findings may help inform medical capabilities of human spaceflight and may also be relevant for terrestrial clinical care such as radiation oncology.

Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients.

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease. PATIENTS AND METHODS: Serum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30). RESULTS: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = -0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups. CONCLUSION: Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

Vascular endothelial growth factor C/A 2578 gene polymorphism and umbilical artery Doppler in preeclamptic women.

INTRODUCTION: Preeclampsia is strongly associated with placental hypoperfusion. Genetic factors have an impact on the pathogenesis of preeclampsia. The aim is to assess the association of Vascular Endothelial Growth Factor (C2578A) gene polymorphism with the occurrence and severity of preeclampsia and the umbilical artery Doppler changes among preeclamptic women. MATERIALS AND METHODS: This case-control study was conducted in clinical and Chemical pathology and Obstetrics departments in Beni- Suef University, Egypt. Two hundred and ninety pregnant women above 20 weeks gestational age until delivery were divided into 2 main groups. The patient group included 145 preeclamptic women who were further sub grouped according to the severity of preeclampsia into 82 severe and 63 mild cases. Control group included 145 normotensive pregnant women. Our primary outcome was detection of VEGF C 2578 A gene mutations by a polymerase chain reaction. A secondary outcome was Doppler changes in the pulsatility index of the umbilical artery compared with VEGF genotypes. RESULTS: Our study showed that VEGF C 2578 A genotype and alleles frequencies were not related to the occurrence of preeclampsia (p-value 0.513 and 0.549, respectively), odds ratio (95%CI) 1.154 (0.724-1.848). Mild preeclamptic cases showed no significance comparing VEGF genotypes studied and pulsatility index of the umbilical artery. However, severe cases showed p-value < 0.0001. CONCLUSION: We concluded that VEGF 2578C/A polymorphism had no association with the occurrence of preeclampsia in studied groups, whereas there was a significant relationship among severe cases between CA and CC genotypes and pulsatility index of the umbilical artery.

Expression of Serum MicroRNAs 221, 222, 15a and Level of VEGF-A in Children with Bronchial Asthma.

Bronchial asthma (BA) remains the most common chronic respiratory disease in children and is characterized by reversible airway obstruction and airway hyperresponsiveness. MicroRNAs (miRNAs) are a class of small, highly conserved non-coding RNA molecules that regulate gene expression at the posttranscriptional level. MiRNAs can either augment or minimize the allergic inflammation in asthma. It has been noted that a group of miRNAs may affect the development of asthma and related inflammatory response. The vascular endothelial growth factor (VEGF) is produced by different types of cells and has a major role in both, physiological and pathological angiogenesis. Our aim was to study serum expression of three microRNAs; 221, 222,15a and Vascular Endothelial Growth Factor A (VEGF-A) levels in children with bronchial asthma. The study included 30 children with BA and a control group of 20 apparently healthy, age and sex matched, children. Quantitative reverse transcription (q RT) polymerase chain reaction (PCR) was performed to examine the expression levels of miR-221, 222 and 15a in patients' sera. Levels of serum VEGF-A were quantified utilizing an ELISA technique. Serum levels of both miRNA-221 and miRNA-222 were not significantly different between pediatric asthmatic patients versus controls (P=0.76 and 0.52, respectively), but showed increase with the disease severity (persistent versus intermittent) (P= 0.09, 0.07, respectively). Serum miRNA-15a expression was significantly down-regulated in asthmatic patients versus the control group (P=0.03). miRNA-15a expression did not differ among various grades of BA (P=0.33) and was not correlated with serum levels of VEGF-A (P=0.56). The level of VEGF-A was significantly increased in serum of pediatrics with bronchial asthma in comparison to the control group (P=0.026). In conclusion, miRNA-15a and VEGF-A may have a role in BA pathogenesis, while miRNA-221 and 222 may reflect BA disease severity.

Association of -308G/A Polymorphism and Serum Level of TNF- α with Bronchial asthma in Children.

Genetic polymorphism of Tumor necrosis factor alpha (TNF-α)-308 G/A is one of the potential markers involved in bronchial asthma pathogenesis. This highly polymorphic gene can influence TNF-α serum levels which has major biological effects on airway inflammation, remodeling, and hyper responsiveness. This study was designed to evaluate the association between TNF-α-308 G/A polymorphism, serum levels of TNF-α and the susceptibility to bronchial asthma in children. The study included 102 pediatric patients with bronchial asthma recruited from Pediatric Allergy and Pulmonology Clinic, Specialized Pediatric Beni Suef University Hospital. Bronchial asthma was classified according to Global Initiative for Asthma (GINA) Guidelines. Moreover, 104 healthy age and sex matched children were enrolled as normal control. Serum TNF-α was measured by ELISA. Analysis of TNF-alpha G308A Polymorphisms was done by allele- specific Polymerase Chain Reaction (PCR). TNF-α level was significantly higher in bronchial asthma patients when compared with the control group, p value 0.001. Individuals with mutant genotype (GA and AA) expressed higher levels of serum TNF-α in comparison to the wild type GG carriers, P value 0.01. The GA genotype frequency of TNF-α-308 G > A polymorphism was significantly higher in patients (34.3%) than (vs.) controls (21.2%) P value 0.028, OR = 2.04; 95% CI = 1.11-3.84. The frequency of combined (AA + GA) genotypes showed a significant difference among cases in comparison with the controls (41.2% vs. 26%), p value 0.027. The pooled OR was 1.99(95% CI=1.1-3.6). In the same context, the A allele was significantly more frequent in asthmatic patients (24%) vs. control (15.4%), P value 0.035 (OR = 1.74, 95% CI = 1.05-2.8) which demonstrated an evidence of possible association between TNF-α-308 G/A polymorphism and bronchial asthma. We concluded that TNF-alpha genetic polymorphisms could have a role in the development of bronchial asthma among Egyptian children.

Resorbable versus titanium plates for orthognathic surgery.

BACKGROUND: Recognition of some of the limitations of titanium plates and screws used for the fixation of bones has led to the development of plates manufactured from bioresorbable materials. Whilst resorbable plates appear to offer clinical advantages over metal plates in orthognathic surgery, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. This review compares the use of titanium versus bioresorbable plates in orthognathic surgery and is an update of the Cochrane Review first published in 2007. OBJECTIVES: To compare the effects of bioresorbable fixation systems with titanium systems used during orthognathic surgery. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 20 January 2017); MEDLINE Ovid (1946 to 20 January 2017); and Embase Ovid (1980 to 20 January 2017). We searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 20 January 2017), and the World Health Organization International Clinical Trials Registry Platform (searched 20 January 2017) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials comparing bioresorbable versus titanium fixation systems used for orthognathic surgery in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We resolved disagreement by discussion. Clinical heterogeneity between the included trials precluded pooling of data, and only a descriptive summary is presented. MAIN RESULTS: This review included two trials, involving 103 participants, one comparing titanium with resorbable plates and screws and the other titanium with resorbable screws. Both studies were at high risk of bias and provided very limited data for the primary outcomes of this review. All participants in one trial suffered mild to moderate postoperative discomfort with no statistically significant difference between the two plating groups at different follow-up times. Mean scores of patient satisfaction were 7.43 to 8.63 (range 0 to 10) with no statistically significant difference between the two groups throughout follow-up. Adverse effects reported in one study were two plate exposures in each group occurring between the third and ninth months. Plate exposures occurred mainly in the posterior maxillary region, except for one titanium plate exposure in the mandibular premolar region. Known causes of infection were associated with loosened screws and wound dehiscence with no statistically significant difference in the infection rate between titanium (3/196), and resorbable (3/165) plates. AUTHORS' CONCLUSIONS: We do not have sufficient evidence to determine if titanium plates or resorbable plates are superior for fixation of bones after orthognathic surgery. This review provides insufficient evidence to show any difference in postoperative pain and discomfort, level of patient satisfaction, plate exposure or infection for plate and screw fixation using either titanium or resorbable materials.

Identifying gaps in research prioritization: The global burden of neglected tropical diseases as reflected in the Cochrane database of systematic reviews.

BACKGROUND: Neglected tropical diseases (NTDs) impact disadvantaged populations in resource-scarce settings. Availability of synthesized evidence is paramount to end this disparity. The aim of the study was to determine whether NTD systematic reviews or protocols in the Cochrane Database of Systematic Reviews (CDSR) reflect disease burden. METHODS: Two authors independently searched the CDSR for reviews/protocols regarding the NTDs diseases. Each review or protocol was classified to a single NTD category. Any discrepancy was solved by consensus with third author. NTD systematic review or protocol from CDSR were matched with disability-adjusted life year (DALY) metrics from the Global Burden of Disease 2010 Study. Spearman's rank correlation coefficient and associated P values were used to assess for correlation between the number of systematic reviews and protocols and the %2010 DALY associated with each NTD. RESULTS: Overall, there was poor correlation between CDSR representation and DALYs. Yellow fever, echinococcus, onchocerciasis, and schistosomiasis representation was well-aligned with DALY. Leprosy, trachoma, dengue, leishmaniasis, and Chagas disease representation was greater, while cysticercosis, human African trypanosomiasis, ascariasis, lymphatic filariasis, and hookworm representation was lower than DALY. Three of the 18 NTDs had reviews/protocols of diagnostic test accuracy. CONCLUSIONS: Our results indicate the need for increased prioritization of systematic reviews on NTDs, particularly diagnostic test accuracy reviews.

Identifying otolaryngology systematic review research gaps: comparing Global Burden of Disease 2010 results with Cochrane Database of Systematic Review content.

IMPORTANCE: Burden of disease should inform research prioritization. OBJECTIVE: To determine whether systematic reviews and protocols published in the Cochrane Database of Systematic Reviews (CDSR) appropriately reflect disease burden for otolaryngologic conditions as measured by the Global Burden of Disease (GBD) 2010 project. DESIGN: Two investigators independently assessed 10 otolaryngologic conditions in CDSR for systematic review and protocol representation from March to June 2014. The otolaryngologic diseases were matched to their respective GBD 2010 disability-adjusted life-years (DALYs) to assess their correlation. MAIN OUTCOMES AND MEASURES: Relationship of CDSR representation (based on systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 10 otolaryngologic conditions. RESULTS: All 10 otolaryngologic conditions were represented by at least 1 systematic review in CDSR. The number of reviews and protocols in CDSR was well matched with GBD 2010 disability metrics for only 1 disease, mouth cancer. Upper respiratory infections, otitis media, thyroid cancer, and cleft lip and cleft palate were overrepresented in CDSR, and esophageal cancer, "other hearing loss," nasopharynx cancer, larynx cancer, and "cancer of other part of pharynx and oropharynx" were underrepresented. CONCLUSIONS AND RELEVANCE: The representation of otolaryngologic conditions in CDSR correlates poorly with DALY metrics. The results of this study may guide future research prioritization and allocation of funds.

Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews.

IMPORTANCE: Research prioritization should be guided by impact of disease. OBJECTIVE: To determine whether systematic reviews and protocol topics in Cochrane Database of Systematic Reviews (CDSR) reflect disease burden, measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 project. DESIGN, SETTING, AND PARTICIPANTS: Two investigators independently assessed 15 skin conditions in the CDSR for systematic review and protocol representation from November 1, 2013, to December 6, 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. An official publication report of all reviews and protocols published by the Cochrane Skin Group (CSG) was also obtained to ensure that no titles were missed. There were no study participants other than the researchers, who worked with databases evaluating CDSR and GBD 2010 skin condition disability data. MAIN OUTCOMES AND MEASURES: Relationship of CDSR topic coverage (systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 15 skin conditions. RESULTS: All 15 skin conditions were represented by at least 1 systematic review in CDSR; 69% of systematic reviews and 67% of protocols by the CSG covered the 15 skin conditions. Comparing the number of reviews/protocols and disability, dermatitis, melanoma, nonmelanoma skin cancer, viral skin diseases, and fungal skin diseases were well matched. Decubitus ulcer, psoriasis, and leprosy demonstrated review/protocol overrepresentation when matched with corresponding DALYs. In comparison, acne vulgaris, bacterial skin diseases, urticaria, pruritus, scabies, cellulitis, and alopecia areata were underrepresented in CDSR when matched with corresponding DALYs. CONCLUSIONS AND RELEVANCE: Degree of representation in CDSR is partly correlated with DALY metrics. The number of published reviews/protocols was well matched with disability metrics for 5 of the 15 studied skin diseases, while 3 skin diseases were overrepresented, and 7 were underrepresented. Our results provide high-quality and transparent data to inform future prioritization decisions.

Oral rinses, mouthwashes and sprays for improving recovery following tonsillectomy.

BACKGROUND: This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 2010 and previously updated in 2011.Tonsillectomy is the surgical removal of lymphoid tissue, the palatine tonsil, which is located at the back of the throat. It is still commonly performed for patients who have recurrent bouts of acute tonsillitis. Although tonsillectomy is considered a fairly minor procedure, pain and bleeding are two of the most common complications; either may delay recovery and can on occasion lead to hospital readmission. Postoperative tonsillectomy medication should provide an adequate reduction in morbidity while minimising side effects, therefore topical agents would seem to be an ideal, safe option. A number of mouthwashes and topical sprays are available which offer pain relief or can help to reduce bleeding in the immediate postoperative period. OBJECTIVES: To assess the effects of oral rinses, mouthwashes and sprays in improving recovery following tonsillectomy. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 4 July 2013. SELECTION CRITERIA: We included randomised controlled trials in which oral rinses, mouthwashes and sprays, used pre- and postoperatively, have been compared with placebo in adults or children undergoing tonsillectomy, with or without adenoidectomy. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion, assessed the risk of bias and extracted data independently. MAIN RESULTS: We included seven trials (593 participants; 397 children and 196 adults). The period of follow-up ranged from 24 hours to two weeks. Few of the trials provided reliable data for the pre-specified primary outcomes and none for the secondary outcomes. The risk of bias was high in most of the included trials. Lidocaine spray appeared to be more effective than saline spray at reducing the severity of pain until the third postoperative day. A small number of participants experienced a burning or stinging sensation with benzydamine spray but not sufficient to discontinue usage. AUTHORS' CONCLUSIONS: Poor reporting quality and inadequate data did not permit comprehensive and reliable conclusions to be made. Future trials should be well-constructed and pay more attention to the methods used to assess outcomes, the timing of the assessments, and the quality of reporting and subsequent analysis of the data.

Carnitine supplementation for inborn errors of metabolism.

BACKGROUND: Inborn errors of metabolism are genetic conditions which can lead to abnormalities in the synthesis and metabolism of proteins, carbohydrates, or fats. It has been proposed that in some instances carnitine supplementation should be provided to infants with a suspected metabolic disease as an interim measure, particularly whilst awaiting test results. Carnitine supplementation is used in the treatment of primary carnitine deficiency, and also where the deficiency is a secondary complication of several inborn errors of metabolism, such as organic acidaemias and fatty acid oxidation defects in children and adults. OBJECTIVES: To assess the effectiveness and safety of carnitine supplementation in the treatment of inborn errors of metabolism. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 4) and MEDLINE via Ovid (1950 to July week 4 2007), LILACS (15/05/2008) and Iranmedex (15/05/2008) and also the reference lists of retrieved articles.Date of most recent search of the Group's Inborn Errors of Metabolism Register: 27 October 2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing carnitine supplementation (in different dose, frequency, or duration) versus placebo in children and adults diagnosed with an inborn error of metabolism. DATA COLLECTION AND ANALYSIS: Two authors independently screened and assessed the eligibility of the identified trials. MAIN RESULTS: No trials were included in the review. AUTHORS' CONCLUSIONS: There are no published or ongoing randomised controlled clinical trials relevant to this review question. Therefore, in the absence of any high level evidence, clinicians should base their decisions on clinical experience and in conjunction with preferences of the individual where appropriate. This does not mean that carnitine is ineffective or should not be used in any inborn error of metabolism. However, given the lack of evidence both on the effectiveness and safety of carnitine and on the necessary dose and frequency to be prescribed, the current prescribing practice should continue to be observed and monitored with care until further evidence is available. Methodologically sound trials, reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement, are required. It should be considered whether placebo-controlled trials in potentially lethal diseases, e.g. carnitine transporter disorder or glutaric aciduria type I, are ethical.

Evidence summary: is smoking cessation an effective and cost-effective service to be introduced in NHS dentistry?

Since August 2009, members of the Primary Care Dentistry Research Forum (www.dentistryresearch.org) have taken part in an online vote to identify questions in day-to-day practice that they felt most needed to be answered with conclusive research. The question that receives the most votes each month forms the subject of a critical appraisal of the relevant literature. Each month a new round of voting takes place to decide which further questions will be reviewed. Dental practitioners and dental care professionals are encouraged to take part in the voting and submit their own questions to be included in the vote by joining the website. The paper below details a summary of the findings of the eighth critical appraisal. In order to address the question raised by the primary care dentistry research forum, first any international study was included that evaluated the effectiveness smoking cessation in dental practice. The aim was to understand whether smoking cessation in dental practice is an effective treatment strategy to increase tobacco cessation and abstinence. Moreover, this rapid assessment intended to identify whether there are certain types of smoking cessation intervention (or components of an intervention) in dental settings that are more effective than the others. In order to determine the applicability of the results to the NHS, we also looked for studies evaluating the cost-effectiveness of these interventions in NHS dentistry, studies reporting the current practice in NHS dentistry and finally qualitative and quantitative studies describing and evaluating the experience and views of dentists in the UK regarding implementing smoking cessation interventions in dental settings. The latter studies would help us to identify the possible barriers and facilitators in implementing these interventions in a dental setting. In conclusion, the critical appraisal of the international literature suggests that behavioural intervention for smoking cessation involving oral health professionals is an effective method of reducing tobacco use in smokers and users of smokeless tobacco and preventing uptake in non-smokers. There is not enough evidence available to assess whether these interventions are cost-effective and the effectiveness of one intervention (or component of the intervention) over another is not clear. The evaluation of the UK-related literature shows that private dental practices deliver more smoking cessation activities than their NHS counterparts. NHS practitioners report lack of reimbursement from the NHS, lack of time and training and fears over patient response as barriers to delivering smoking cessation interventions. We did not find studies evaluating the cost-effectiveness of the intervention in the UK.

Hand and ultrasonic instrumentation for orthograde root canal treatment of permanent teeth

Root canal treatment is a frequently performed dental procedure and is carried out on teeth in which irreversible pulpitis has led to necrosis of the dental pulp. Removal of the necrotic tissue remnants and cleaning and shaping of the root canal are important phases of root canal treatment. Treatment options include the use of hand and rotary instruments and methods using ultrasonic or sonic equipment. OBJECTIVES: The objectives of this systematic review of randomized controlled trials were to determine the relative clinical effectiveness of hand instrumentation versus ultrasonic instrumentation alone or in conjunction with hand instrumentation for orthograde root canal treatment of permanent teeth. MATERIAL AND METHODS: The search strategy retrieved 226 references from the Cochrane Oral Health Group Trials Register (7), the Cochrane Central Register of Controlled Trials (CENTRAL) (12), MEDLINE (192), EMBASE (8) and LILACS (7). No language restriction was applied. The last electronic search was conducted on December 13th, 2007. Screening of eligible studies was conducted in duplicate and independently. RESULTS: Results were to be expressed as fixed-effect or random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95 percent confdence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. No eligible randomized controlled trials were identifed. CONCLUSIONS: This review illustrates the current lack of published or ongoing randomized controlled trials and the unavailability of high-level evidence based on clinically relevant outcomes referring to the effectiveness of ultrasonic instrumentation used alone or as an adjunct to hand instrumentation for orthograde root canal treatment. In the absence of reliable research-based evidence, clinicians should base their decisions on clinical experience, individual circumstances and in conjunction with patients' preferences where appropriate. Future randomized controlled trials might focus more closely on evaluating the effectiveness of combinations of these interventions with an emphasis on not only clinically relevant, but also patient-centered outcomes.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

INTRODUCTION: Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. OBJECTIVE: The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. MATERIAL AND METHODS: Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. RESULTS: The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3 percent) or concealment of the allocation sequence (84.2 percent). Participants and outcome assessors were reported as blinded in only 31.2 percent of the reports. Withdrawals and losses were only clearly described in 6.5 percent of the reports and none mentioned an intention-to-treat analysis or any similar ...

Comparative effectiveness research and evidence-based health policy: experience from four countries.

CONTEXT: The discussion about improving the efficiency, quality, and long-term sustainability of the U.S. health care system is increasingly focusing on the need to provide better evidence for decision making through comparative effectiveness research (CER). In recent years, several other countries have established agencies to evaluate health technologies and broader management strategies to inform health care policy decisions. This article reviews experiences from Britain, France, Australia, and Germany. METHODS: This article draws on the experience of senior technical and administrative staff in setting up and running the CER entities studied. Besides reviewing the agencies' websites, legal framework documents, and informal interviews with key stakeholders, this analysis was informed by a workshop bringing together U.S. and international experts. FINDINGS: This article builds a matrix of features identified from the international models studied that offer insights into near-term decisions about the location, design, and function of a U.S.-based CER entity. While each country has developed a CER capacity unique to its health system, elements such as the inclusiveness of relevant stakeholders, transparency in operation, independence of the central government and other interests, and adaptability to a changing environment are prerequisites for these entities' successful operation. CONCLUSIONS: While the CER entities evolved separately and have different responsibilities, they have adopted a set of core structural, technical, and procedural principles, including mechanisms for engaging with stakeholders, governance and oversight arrangements, and explicit methodologies for analyzing evidence, to ensure a high-quality product that is relevant to their system.

Carnitine supplementation for inborn errors of metabolism.

BACKGROUND: Inborn errors of metabolism are genetic conditions which can lead to abnormalities in the synthesis and metabolism of proteins, carbohydrates, or fats. It has been proposed that in some instances carnitine supplementation should be provided to infants with a suspected metabolic disease as an interim measure, particularly whilst awaiting test results. Carnitine supplementation is used in the treatment of primary carnitine deficiency, and also where the deficiency is a secondary complication of several inborn errors of metabolism, such as organic acidaemias and fatty acid oxidation defects in children and adults. OBJECTIVES: To assess the effectiveness and safety of carnitine supplementation in the treatment of inborn errors of metabolism. SEARCH STRATEGY: We searched the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 4) and MEDLINE via Ovid (1950 to July week 4 2007), LILACS (15/05/2008) and Iranmedex (15/05/2008) and also the reference lists of retrieved articles.Date of most recent search of the Group's Inborn Errors of Metabolism Register: 27 October 2008. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing carnitine supplementation (in different dose, frequency, or duration) versus placebo in children and adults diagnosed with an inborn error of metabolism. DATA COLLECTION AND ANALYSIS: Two authors independently screened and assessed the eligibility of the identified trials. MAIN RESULTS: No trials were included in the review. AUTHORS' CONCLUSIONS: There are no published or ongoing randomised controlled clinical trials relevant to this review question. Therefore, in the absence of any high level evidence, clinicians should base their decisions on clinical experience and in conjunction with preferences of the individual where appropriate. This does not mean that carnitine is ineffective or should not be used in any inborn error of metabolism. However, given the lack of evidence both on the effectiveness and safety of carnitine and on the necessary dose and frequency to be prescribed, the current prescribing practice should continue to be observed and monitored with care until further evidence is available. Methodologically sound trials, reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement, are required. It should be considered whether placebo-controlled trials in potentially lethal diseases, e.g. carnitine transporter disorder or glutaric aciduria type I, are ethical.

Resorbable versus titanium plates for facial fractures.

BACKGROUND: Rigid internal fixation of the jaw bones is a routine procedure for the management of facial fractures. Titanium plates and screws are routinely used for this purpose. The limitations of this system has led to the development of plates manufactured from bioresorbable materials which, in some cases, omits the necessity for the second surgery. However, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. OBJECTIVES: To compare the effectiveness of bioresorbable fixation systems with titanium systems for the management of facial fractures. SEARCH STRATEGY: We searched the following databases: The Cochrane Oral Health Group's Trials Register (to 20th August 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to 20th August 2008), EMBASE (from 1980 to 20th August 2008), http://www.clinicaltrials.gov/ and http://www.controlled-trials.com (to 20th August 2008). SELECTION CRITERIA: Randomised controlled trials comparing resorbable versus titanium fixation systems used for facial fractures. DATA COLLECTION AND ANALYSIS: Retrieved studies were independently screened by two review authors. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. MAIN RESULTS: The search strategy retrieved 53 potentially eligible studies. None of the retrieved studies met our inclusion criteria and all were excluded from this review. One study is awaiting classification as we failed to obtain the full text copy. Three ongoing trials were retrieved, two of which were stopped before recruiting the planned number of participants. In one study, the excess complications in the resorbable arm was declared as the reason for stopping the trial. AUTHORS' CONCLUSIONS: This review illustrates that there are no published randomised controlled clinical trials relevant to this review question. There is currently insufficient evidence for the effectiveness of resorbable fixation systems compared with conventional titanium systems for facial fractures. The findings of this review, based on the results of the aborted trials, do not suggest that resorbable plates are as effective as titanium plates. In future, the results of ongoing clinical trials may provide high level reliable evidence for assisting clinicians and patients for decision making. Trialists should design their studies accurately and comprehensively to meet the aims and objectives defined for the study.