Sound Trials Research Articles

Priorities and funding for research in intellectual disabilities

Priorities and funding for research in intellectual disabilities

Adherence to Transfusion Protocols and the Use of Recombinant Activated Factor VII.

Abstract 4192 BackgroundMost hospitals have clinical guidelines for the off-label use of recombinant activated Factor VII (rFVIIa, Novoseven), primarily as part of a massive transfusion protocol. Over the past years rFVIIa has increasingly been used outside the approved indications in haemophilia with inhibitors and Glanzmann's Thrombasthenia, particularly in trauma, cardiac surgery and other critical bleeding episodes. Use in these areas remains controversial. MethodsMonash University established the Haemostasis Registry in 2005 (with an educational grant from NovoNordisk Pharmaceuticals) to monitor the use of rFVIIa throughout Australia and New Zealand. More than 95 hospitals are contributing data to the Registry including all major users of rFVIIa in Australia and New Zealand. As part of the process of joining the Registry project, participating hospitals are asked to supply copies of their protocols for use of rFVIIa. ResultsApproximately 3000 cases of rFVIIa use have been reported to the Register. Major areas of use are cardiac surgery (∼ 41%), other surgery (∼17%) and trauma (∼15%). The majority(77.3%) of hospitals have documented protocols for rFVIIa use. Many of these are similar and are centred around situations of massive transfusion. However, 64.5% of cases of rFVIIa use submitted to the Haemostasis Registry, from hospitals where protocols exist, do not conform with the numerical components of these protocols. ConclusionsThis is the largest dataset of rFVIIa cases published to date and can now provide greater insight into the actual rather than theoretical use of rFVIIa in Australia and New Zealand. Lack of compliance with hospital protocols for rFVIIa use indicates either that the protocols do not reflect actual and appropriate use or that clinicians need to be further educated regarding what is currently considered appropriate use. In the absence of sound clinical trial evidence, consensus regarding appropriate use has not been achieved. In these circumstances, data from the Haemostasis Registry continues to be important in elucidating the safety and efficacy of rFVIIa and providing important feedback to doctors and hospitals.The Haemostasis Registry is funded through an unrestricted Educational Grant from NovoNordisk Pharmaceuticals Pty Ltd. None of the authors have a financial interest in the outcomes of the study. Disclosures:Off Label Use: Recombinant activated Factor VII (rFVIIa, Novoseven). FVIIa is a naturally occurring initiator of haemostasis. Its recombinant form, rFVIIa, is approved for the treatment of spontaneous & surgical bleeding in patients with haemophilia A or B and with antibodies to either factor VIII or factor IX. It has been extensively used amongst haemophiliacs and appears to enhance clotting at the site of bleeding without systemic activation of the coagulation cascade At high doses rFVIIa binds to the surface of activated platelets and initiates the coagulation cascade at these sites Recently various case series and case reports have reported the efficacy of rFVIIa in patients with life-threatening bleeding in patients with coagulation disturbances but without coagulation inhibitors.

Expanding Treatment Options for Cocaine Dependence

Expanding Treatment Options for Cocaine Dependence

2008 Emily Cooley Memorial Lecture: lessons learned from pediatric transfusion medicine clinical trials . . . a little child shall lead them

Many clinical practices in transfusion medicine are controversial and/or lack definitive guidelines established by sound clinical trials. Although recommendations based on results of clinical trials performed using infants and children may not always be applied directly to adults--and vice versa--lessons learned from pediatric trials can be useful when critically assessing the design/results/conclusions of adult trials. Four randomized clinical trials (RCTs) studying pediatric patients were critically reviewed. They addressed two red blood cell (RBC) transfusion issues: 1) transfusion guidelines by which RBC transfusions are "triggered" by liberal (LIB; high pretransfusion patient hematocrit [Hct] levels) versus being "triggered" by restricted (RES; low pretransfusion Hct levels) and 2) transfusion of fresh RBCs (<or=7 days' storage) versus RBCs (up to 42 days' storage). Findings established by primary outcomes generally were firm (e.g., fewer RBC transfusions were given to infants/children managed by RES guidelines; transfusing small volumes of RBCs stored up to 42 days to preterm infants diminished allogeneic donor exposures and were equally efficacious and safe as fresh RBCs stored <or=7 days). Findings based on secondary outcomes, subset, and post hoc analyses were inconsistent (e.g., clinical outcomes were equivalent after LIB or RES transfusions in only two of three RCTs; in the third, more neurologic problems were found in neonates given RES transfusions). Clinical practices should be based on data pertaining to the primary outcomes of RCTs, because trials are designed and statistically powered to address these issues. Clinical practices suggested by analysis of secondary outcomes, subsets of patients, and post hoc analyses should be applied cautiously until studied further-ideally, as primary outcomes in subsequent RCTs.

Verbal and nonverbal semantic processing in children with developmental language impairment.

In an effort to clarify whether semantic integration is impaired in verbal and nonverbal auditory domains in children with developmental language impairment (a.k.a., LI and SLI), the present study obtained behavioral and neural responses to words and environmental sounds in children with language impairment and their typically developing age-matched controls (ages 7-15 years). Event-related brain potentials (ERPs) were recorded while children performed a forced-choice matching task on semantically matching and mismatching visual-auditory, picture-word and picture-environmental sound pairs. Behavioral accuracy and reaction time measures were similar for both groups of children, with environmental sounds eliciting more accurate responses than words. In picture-environmental sound trials, behavioral performance and the brain's response to semantic incongruency (i.e., the N400 effect) of the children with language impairment were comparable to those of their typically developing peers. However, in picture-word trials, children with LI tended to be less accurate than their controls and their N400 effect was significantly delayed in latency. Thus, the children with LI demonstrated a semantic integration deficit that was somewhat specific to the verbal domain. The particular finding of a delayed N400 effect is consistent with the storage deficit hypothesis of language impairment (Kail & Leonard, 1986) suggesting weakened and/or less efficient connections within the language networks of children with LI.

Evidenzbasierte Medizin und Ultraschalltherapie des Skeletts

The aim of this review is to critically analyze the evidence of therapeutic ultrasound between 0.8 and 3 MHz for treating musculoskeletal diseases. Relevant randomized, controlled, clinical trials and systematic reviews published on this topic have been taken into consideration.There was evidence of effectiveness for the following indications: inflammatory and degenerative diseases of joints and the vertebral column, overuse syndromes of tendons and muscles and the facilitation of bone tissue healing.According to the current knowledge an evidence-based recommendation could be most clearly made for the facilitation of bone fracture healing with ultrasound. For all other indications evidence was based on overly sparse data from low quality randomized controlled trials that would not allow clear recommendations. However, there is also a lack of data from methodologically sound clinical trials that could have proven the inefficacy of this treatment. As beneficial effects with ultrasound are frequently observed in everyday clinical practice, this therapeutic modality should continue to be considered in the future as a treatment option for musculoskeletal diseases.

Evaluation of PubMed filters used for evidence-based searching: validation using relative recall

The research sought to determine the value of PubMed filters and combinations of filters in literature selected for systematic reviews on therapy-related clinical questions. References to 35,281 included and 48,514 excluded articles were extracted from 2,629 reviews published prior to January 2008 in the Cochrane Database of Systematic Reviews and sent to PubMed with and without filters. Sensitivity, specificity, and precision were calculated from the percentages of unfiltered and filtered references retrieved for each review and averaged over all reviews. Sensitivity of the Sensitive Clinical Queries filter was reasonable (92.7%, 92.1-93.3); specificity (16.1%, 15.1-17.1) and precision were low (49.5%, 48.5-50.5). The Specific Clinical Queries and the Single Term Medline Specific filters performed comparably (sensitivity, 78.2%, 77.2-79.2 vs. 78.0%; 77.0-79.0; specificity, 52.0%, 50.8-53.2 vs. 52.3%, 51.1-53.5; precision, 60.4%, 59.4-61.4 vs. 60.6%, 59.6-61.6). Combining the Abridged Index Medicus (AIM) and Single Term Medline Specific (65.2%, 63.8-66.6), Two Terms Medline Optimized (64.2%, 62.8-65.6), or Specific Clinical Queries filters (65.0%, 63.6-66.4) yielded the highest precision. Sensitive and Specific Clinical Queries filters used to answer questions about therapy will result in a list of clinical trials but cannot be expected to identify only methodologically sound trials. The Specific Clinical Queries filters are not suitable for questions regarding therapy that cannot be answered with randomized controlled trials. Combining AIM with specific PubMed filters yields the highest precision in the Cochrane dataset.

Attention to speech sounds in normal-hearing and deaf children with cochlear implants.

Cochlear implantation (CI) is a treatment for severe-to-profound hearing loss in congenitally deaf children. Although there is very little variability in auditory thresholds among CI recipients, there is a large amount of variability in language outcomes. One possible source of variability in language outcomes is individual differences in attention and cognitive processes, which may be affected by early auditory deprivation. The effect of auditory deprivation on attention to auditory input was investigated by comparing attention to speech sounds in 23 young deaf children with CIs and 23 normal-hearing age-match controls. The deaf children received their CIs between 6 and 23 months and were tested several times during the first 1.5 years after implantation. Participants were seated on their caregiver’s lap in front of a TV monitor. On each trial, they were presented with a checkerboard pattern and either silence or a repeating speech sound. Normal-hearing children looked longer at the checkerboard during the sound trials at the youngest ages whereas CI children were delayed in showing a preference for the sound trials. Moreover, performance on this task correlated with language outcome measures taken two years later, suggesting that attention to speech sounds after implantation is predictive of later language development.

The treatment of depression in patients with advanced cancer undergoing palliative care

Depression is a common condition affecting those with advanced cancer, but evidence for effective treatment has been sparse. In recent years, there has been a welcome increase in research activity, with both pharmacological and nonpharmacological treatments being trialled. This review assesses recent studies of pharmacological interventions including antidepressants and psychostimulants and nonpharmacological interventions including cognitive behavioural therapy, supportive expressive group therapy, couples therapy, complex interventions and aromatherapy massage for treatment of depression. Recent published systematic reviews of interventions for depression are also discussed. Recent research efforts have paid particular attention to psychological interventions, with cognitive behavioural therapy approaches being most evaluated and showing some encouraging results. Pharmacological interventions remain challenging to assess using rigorous clinical trial methodology, and clinicians still rely upon data derived from studies using general populations and those with less advanced disease or other physical illness. Methodologically sound trials of pharmacological interventions for treatment of depression in advanced disease remains an area of research need.

Systematic review of clinical trials of acupuncture‐related therapies for primary dysmenorrhea

Acupuncture-related therapies might be an effective intervention for primary dysmenorrhea. To evaluate the effects of acupuncture-related therapies for treating primary dysmenorrhea. A specified literature search was performed of the Cochrane Library, MEDLINE, EMBASE, CNKI, and CBM databases. All clinical controlled trials pertaining to acupuncture-related therapies for primary dysmenorrhea were included, and the quality of the trials was assessed. Two independent reviewers were responsible for data extraction and assessment. The original data of each trial were analyzed with software (Revman 4.2), but a meta-analysis could not be carried out because of the heterogeneity of the trials. Thirty randomized controlled trails (RCTs) and two controlled clinical trials (CCTs) were identified. Most of the trials were of low methodologic quality (six trials were Grade B and 26 trials were Grade C). Data analysis indicated that there were conflicting results regarding whether acupuncture-related therapies were more effective than control treatments. However, there was a small, methodologic sound trial of acupuncture which suggested that acupuncture was more effective than control groups (placebo acupuncture: WMD=-0.57 and 95% CI=-0.76-0.38; standard control: WMD=-.19 and 95% CI=-0.37-0.01; visitation control: WMD=-1.04 and 95% CI=-1.28-0.80). Because of low methodologic quality and small sample size, there is no convincing evidence for acupuncture in the treatment of primary dysmenorrhea. There is an urgent need for randomized, blinded, placebo-controlled trials to assess the effects of acupuncture.

Reply to Improved Survival With Adjuvant External-Beam Radiation Therapy in Lymph Node-Negative Pancreatic Cancer

We appreciate the opportunity to reply to Dr. Chu's comments. We acknowledge that selection bias is a concern for retrospective studies. However, bias does not necessarily detract from their value; such studies can address and answer important questions. We attempted to limit selection bias in our report1 by removing early deaths. This adjustment does not entirely eliminate selection bias and is not equivalent to the randomization necessary to definitively prove the benefits of adjuvant radiation. To this end, we indicated in our report, rather, that adjuvant radiation therapy clearly has no survival disadvantage, an outcome less prone to selection or statistical bias.1 This conclusion is noteworthy in light of the findings of the European Study Group for Pancreatic Cancer (ESPAC-1) trial.2 We read with great interest the study conducted by Hazard et al.3 However, there were notable differences in their methodology compared with ours. First, Hazard et al investigated patients who received neoadjuvant and/or adjuvant radiation therapy, whereas we limited our study to patients who received adjuvant external–beam radiation. Second, Hazard et al described the extent of disease using the American Joint Committee on Cancer (AJCC) staging system by incorporating both T and N classifications. Therefore, early–stage disease was categorized as T1-T2N0M0, whereas the T3-T4N0M0 group was comprised of patients with direct extension of disease. Additional groups included patients with lymph node–positive disease (regardless of T classification) and patients with disease with both direct extension and lymph node positivity. Using this stratification, Hazard et al concluded that radiation therapy was advantageous in patients with direct extension and/or regional lymph node involvement with respect to overall survival, and advantageous in patients with lymph node–positive disease and disease with both direct extension and lymph node positivity with respect to cause–specific survival. Similarly, our study demonstrated that the primary benefit of radiation therapy with respect to overall survival was noted in the group of patients with T3N0 disease. As such, the findings of our study1 and those of Hazard et al3 are not necessarily contradictory. Furthermore, we agree that the adequate retrieval and identification of lymph nodes may be relevant in the accurate staging and classification of patients with pancreatic cancer.4 In summary, our study and that of Hazard et al1, 3 suggest that adjuvant radiation therapy may improve survival in all patients who have undergone curative surgery for pancreatic cancer. We advocate the implementation of methodologically sound prospective trials to definitively prove our conclusions. Avo Artinyan MD, MS*, Joseph Kim MD*, * Department of General Oncology Surgery, City of Hope, National Medical Center, Duarte, California.

Drug development in neuropsychopharmacology

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

Ethics of Clinical Trials

Although clinical trials are conducted far more ethically and safer now than they were some decades ago, the elimination of gross abuses has tended to highlight more subtle ethical problems. Therefore, research in man, especially clinical drug trials, must now take into account ethical and legal requirements. This review examines the progress of clinical trial ethics, highlights the major ethical principles and challenges involved in the conduct of clinical trials, and suggests measures to ensure scientifically and ethically sound clinical trials. An internet search and a perusal of the literature on the history of clinical trials, medical ethics and good clinical practice, reveal that apart from laying a general principle, the Oath of Hippocrates did not provide a guide on the specific ethical problems involved in undertaking research, an important arm of advancement in medical knowledge. Hence, to avert continued ethical abuses of subjects during clinical research, the current reference guideliNe--the Helsinki Declaration of 1964 (revised in 1975), was adopted by the World Medical Assembly. It emphasized four major principles: autonomy, nonmaleficience, beneficence and justice. In applying these principles, the researcher must obtain a written free and well informed consent from patients who should be aware of their right to withdraw from trial at any moment. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. He must ethically monitor and assess risks and benefits of the trial throughout its duration and use a fair procedure in selecting research subjects and must respect the concept of inviolability of the human person. Ethical challenges confronting clinical trials include the appropriateness of the proposed research, obtaining free informed consent, use of medications after completion of drug trials, drug toxicities and long-term side effects as well as the release and publication of research result. To improve protection for research subjects and have ethically sound clinical trials, there is need to adhere to global standards and legislations; establish, strengthen and empower regulatory bodies; develop partnership among stakeholders; intensify public enlightenment and train research personnel.

A selective representation of the meaning of actions in the auditory mirror system

Mirror neurons in the monkey's premotor cortex respond during both execution and observation of actions and are thought to be critical for understanding others' actions. Human studies have shown premotor cortex activation while viewing actions, hearing their sounds, listening to or reading action-related sentences, and have compared execution and observation of similar actions. However, we still lack direct evidence in humans of the most striking and theoretically relevant feature of mirror neurons, i.e., that they map seen/heard actions onto motor representations of the same actions at an abstract level. Here we combine fast event-related functional magnetic resonance imaging with an unconscious semantic priming paradigm and show that the human auditory mirror system also holds an abstract representation of the meaning of heard actions. We analyzed the effect on brain activity of trial-by-trial semantic congruency between a target sound denoting a hand or mouth action (or an environmental event) and a briefly flashed written word acting as an unconscious cross-modal prime. Left inferior frontal and posterior temporal regions selectively responded to action sounds in a non-somatotopic fashion and were modulated by semantic congruency only in action sound trials. We also observed regions selective for either hand or mouth actions, which however did not show a corresponding effector-specific effect of semantic congruency. These results provide evidence that the human mirror system represents the meaning of actions (but not of other events) (a) at an abstract, semantic level, (b) independently of the effector, and (c) independently of conscious awareness.

Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip

Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. To determine the effects of chondroitin on pain in patients with osteoarthritis. The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

L’essai clinique contrôlé randomisé

It is generally agreed that the first comparative clinical trial in history was done by James Lind in 1747, in the treatment of scurvy. The general bases of modern experimental medicine were published by Claude Bernard in 1865. However, it is the development of new drugs and the evolution of methodological concepts that led to the first randomized controlled clinical trial, in 1948, which showed that the effects of streptomycin on pulmonary tuberculosis were significantly different from those of a placebo. Today, "evidence-based" medicine aims to rationalize the medical decision-making process by taking into account, first and foremost, the results of controlled randomized clinical trials, which provide the highest level of evidence. In the second half of the 20th century it became clear that different kinds of clinical trials might not provide the same level of evidence. Practitioners' intimate convictions must be challenged by the results of controlled clinical trials. Take the CAST trial for example, which, in 1989, tested antiarrhythmic drugs versus placebo in patients with myocardial infarction. It was well known that ventricular arrhythmias were a factor of poor prognosis in coronary heart disease, and it was therefore considered self-evident that drug suppression of these ventricular arrhythmias would reduce the mortality rate. In the event, the CAST trial showed the exact opposite, with an almost 3-fold increase in total mortality among patients with coronary heart disease who were treated with antiarrhythmic drugs. These results had a profound impact on the use of antiarrythmic drugs, which became contraindicated after myocardial infarction. A clinical trial has to fulfill certain methodological standards to be accepted as evidence-based medicine. First, a working hypothesis has to be formulated, and then the primary outcome measure must be chosen before beginning the study. An appropriate major endpoint for efficacy must be selected, in keeping with the primary outcome. One may choose either a single endpoint (for instance all-cause mortality; or a composite criterion taking into account various manifestations of the same health disorder (for instance cardiovascular mortality plus non lethal myocardial infarction plus non lethal ischemic stroke). The trial must be controlled, i.e. must compare the intervention with a standard or dummy treatment. A randomization process is used to ensure that the groups are comparable. The patients must be monitored and the results analyzed in double-blind manner The required number of patients is calculated based on the working hypothesis ("superiority" trial or "equivalence" trial), as well as the spontaneous variability of the main endpoint, and the alpha and beta statistical risks. The experimental design (cross-over or parallel groups) is chosen according to the primary outcome measure and the disease characteristics. Finally, the results must be analyzed in an intention-to-treat manner, taking into account all the patients who were initially randomized. The results of these methodologically sound trials form the basis for official therapeutic guidelines, which help physicians to choose the best treatments for their patients. However, extrapolating the results of randomized controlled clinical trials to the general patient population is not always straightforward. For instance, it is well known that patients who participate in clinical trials are highly selected and therefore somewhat unrepresentative. In addition, their numbers are limited and the treatment period is often much shorter than in routine management of a chronic disease. Finally, patients in clinical trials are monitored more closely than in routine practice. This is why we need post-marketing pharmacoepidemiological studies, in which cohorts of patients exposed to the treatment in question are monitored sufficiently long to determine the precise risk-benefit ratio. Controlled clinical trials are lacking in various fields of biomedical research, either because drug companies consider them unprofitable, or because they concern public health issues that are outside the scope of the private sector In such cases, controlled clinical trials must be undertaken and funded by the public sector Today, only North American institutions such as NIH and the National Heart Blood and Lung Institute are capable of sponsoring such trials. This creates a potential problem for extrapolation to European patient populations, which may be different. Large controlled clinical trials must start to be sponsored by public funding in Europe if European practitioners are to receive the evidence-based results they need to rationalize their medical practice.

Poor-Prognosis Germ Cell Tumors: We Have Not Yet Crossed the Finish Line

Poor-Prognosis Germ Cell Tumors: We Have Not Yet Crossed the Finish Line

Effects of Acupuncture As A Treatment for Hyperventilation Syndrome: A Pilot, Randomized Crossover Trial

Sustained and subtle hyperventilation can result in a wide variety of symptoms, leading to a chronic condition that has been termed hyperventilation syndrome (HVS). Treatment options include physiotherapy, in the form of breathing retraining (BR), but additional approaches aim to reduce the anxiety that is recognized as being a frequent component of this condition. The aim of this study was to evaluate whether acupuncture is an appropriate treatment for HVS to reduce anxiety, and whether a crossover trial is an appropriate study design to evaluate acupuncture in this condition. A single-blind crossover trial was carried out comparing the effects of 4 weeks (30 minutes twice weekly) acupuncture and BR on patients with HVS. Ten (10) patients diagnosed with HVS were recruited to the trial and randomized into two groups. Both groups received acupuncture and BR with a washout period of 1 week. The primary outcome measure used was the Hospital Anxiety and Depression (HAD) Scale. Other outcome measures used were the Nijmegen questionnaire and Medical Research Council Dyspnea scale. The results showed statistically significant treatment differences between acupuncture and breathing retraining, in favor of acupuncture. Reductions were found in the HAD A (anxiety) (p = 0.02) and Nijmegen (symptoms) (p = 0.03) scores. There was no statistical evidence of any carryover effects. However, when graphically examining individual anxiety scores, in those who received acupuncture first, there was a reduction in anxiety levels which persisted through the washout period, suggesting that there may have been some carryover effect from this treatment. This study suggests that acupuncture may be beneficial in the management of HVS in terms of reducing anxiety levels and symptom severity. However, there may be some carryover effect, after acupuncture treatment, which went undetected because the small sample size. This preliminary study provides the basis for a larger, sufficiently powered and methodologically sound trial.

A Cochrane Systematic Review Finds No Evidence to Support the Use of Antibiotics for Pain Relief in Irreversible Pulpitis

The Cochrane Systematic Review promotes evidence-based outcomes studies. The review summarized here was conducted in an attempt to achieve reliable evidence concerning the effectiveness, or otherwise, of prescribing antibiotics for patients having irreversible pulpitis. A competent search strategy was developed and used across several databases including MEDLINE to identify randomized controlled trials for inclusion. Assessment of methodological quality was based on criteria defined by The Cochrane Collaboration. Clinical outcome, expressed in terms of pain relief, was examined. There was a relative dearth of research providing a high level of evidence. Only one methodologically sound trial was found that compared pain relief with systemic antibiotic/analgesic treatment against a placebo/analgesic combination during the acute preoperative phase of irreversible pulpitis. Although the selected study used a relatively small, low-powered sample, it did provide some evidence that there is no significant difference in pain relief for patients with untreated irreversible pulpitis who received antibiotics versus those who did not. These findings increase the rationale to investigate the teaching of safe and effective antibiotic prescribing in endodontics and to advance the development of appropriate evidence-based clinical guidelines.

Manual Therapy for Patients With Stable Angina Pectoris: A Nonrandomized Open Prospective Trial

To examine if participants with chest pain originating from the spine would benefit from manual therapy. A nonrandomized, open, prospective trial was performed at a tertiary hospital. Patients who were referred for coronary angiography because of known or suspected stable angina pectoris were invited to participate in this study. A total of 275 took part, 50 were diagnosed as cervicothoracic angina (CTA)-positive (chest pain from the cervicothoracic spine) and 225 as CTA-negative. The intervention performed was manual therapy according to chiropractic standards. Patient self reported questionnaires at baseline and 4-week follow-up, including pain measured with an 11-point box scale, Short Form 36 (quality of life), and perceived improvement. Approximately 75% of CTA-positive patients reported improvement of pain and of general health after treatment, compared with 22% to 25% of CTA-negative patients (P < .0001). Pain intensity decreased in both groups with consistently larger decreases for all measures of pain among CTA-positive patients. Short Form 36 scores increased in the CTA-positive group in 5 of 8 scales and remained unchanged in the CTA-negative group. This study suggested that patients with known or suspected angina pectoris and a diagnosis of CTA may benefit from chiropractic manual therapy. Methodologically, sound randomized clinical trials are needed to corroborate our results.