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Many microbiome analysis techniques can only detect the microbes present in the reference genome database used. In this issue of Cell Host & Microbe, Cha et al. establish an improved genome database of the human oral microbiome, which they use to discover a connection between periodontitis and an enigmatic bacterial phylum.
PURPOSE: To assess the effectiveness of SRS alone or in combination with WBRT compared to surgery and/or WBRT in prolonging survival and improving the quality-of-life and functional status of patients with brain metastases. METHODS AND MATERIALS: A meta-analysis of randomized controlled trials and concurrent cohort studies examining SRS versus SRS + WBRT, SRS versus WBRT +/- surgical resection, SRS versus surgical resection only, or SRS + WBRT versus WBRT was conducted. Trial registers, bibliographic databases, and reference lists from selected studies and recent issues of relevant journals were searched. Neuro-oncology specialists were also contacted. All studies were analyzed independently by two reviewers, applying validated critical appraisal techniques. RESULTS: The review identified three RCTs and one cohort study. Among patients with multiple metastases, no difference in survival between those treated with WBRT + SRS and those treated with WBRT was found. However, in patients with one metastasis, a statistically significant difference, favoring those treated with WBRT + SRS, was observed. Regarding local tumor control at 24 months, rates were significantly higher in the WBRT + SRS treatment arm, regardless of the number of metastases. CONCLUSIONS: Adding SRS to WBRT improves survival in patients with one brain metastasis. Combining SRS and WBRT improves local tumour control and functional independence in all patients.
BACKGROUND: The growing global burden of heart failure (HF) necessitates the investigation of alternative methods of providing co-ordinated, integrated and client-focused primary care. Currently, the models of nurse-coordinated care demonstrated to be effective in randomized controlled trials are only available to a relative minority of clients and their families with HF. This current gap in service provision could prove fertile ground for the expansion of practice nursing [The Nurse in Family Practice: Practice Nurses and Nurse Practitioners in primary health care. 1988, Scutari Press, London: Impact of rural living on the experience of chronic illness. Australian Journal of Rural Health, 2001. 9: 235-240]. AIM: This paper aims to review the published literature describing the current and potential role of the practice nurse in HF management in Australia. METHODS: Searches of electronic databases, the reference lists of published materials and the internet were conducted using key words including 'Australia', 'practice nurse', 'office nurse', 'nurs*', 'heart failure', 'cardiac' and 'chronic illness'. Inclusion criteria for this review were English language literature; nursing interventions for heart failure (HF) and the role of practice nurses in primary care. RESULTS: There is currently a paucity of data evaluating the potential role for practice nurses in a reconfigured, collaborative health care system. Those studies that were identified were, largely, of a descriptive nature. In addition to identifying the practice nurse as a largely unexplored resource, key themes that emerged from the review include: (1) current general practice services face significant barriers to the implementation of evidence-based HF practice; (2) there is considerable variation in the practice nurse role between general practices; (3) there are significant barriers to the expansion of the practice nurse role; (4) multidisciplinary interventions can effectively deliver secondary prevention strategies; (5) practice nurses can potentially facilitate these multidisciplinary interventions; and (6) practice nurses are favorably perceived by consumers although there is some confusion about the nature of their role. CONCLUSION: On the basis of this literature review, practice nurses represent a potentially useful adjunct to current models of service provision in HF management. Further research needs to comprehensively investigate the role of the practice nurse in the Australian context with a view to developing effective and sustainable frameworks for clinical practice. In particular, high-level evidence is required to evaluate the efficacy of the practice nurse role compared to current disease management strategies.
OBJECTIVE: Review of literature with regard to androgen replacement therapy in women. DESIGN: Review of the MEDLINE database and references from articles. CONCLUSIONS: Androgens affect sexual function, bone health, muscle mass, body composition, mood, energy, and the sense of well-being. Androgen insufficiency clearly has been demonstrated in patients with hypopituitarism, adrenalectomy, oophorectomy, and in some women placed on oral estrogen therapy which increases sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable forms of T. Symptoms of androgen insufficiency in women may include a diminished sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder with decreased libido, or decreased sexual receptivity and pleasure that causes a great deal of personal distress. The preponderance of evidence from clinical trials supports the correlation of decreased endogenous androgen levels with these symptoms and alleviation of many of the symptoms with the administration of T or, in some cases, DHEA. There are no Food and Drug Administration-approved androgen preparations on the market for treating androgen insufficiency in women. The safety profile of androgens in doses used for the treatment of hypoactive sexual desire disorder has been excellent with only mild acne and hirsutism being noted in a minority of patients.
BACKGROUND: This review was undertaken to assess the effectiveness of management strategies for sexual dysfunction caused by antidepressant medication. METHODS: Electronic databases and reference lists were searched, and pharmaceutical companies and experts contacted to identify randomised controlled trials comparing management strategies for antidepressant-induced sexual dysfunction. RESULTS: Fifteen trials involving 904 people were included. One trial involving 75 people with sexual dysfunction due to sertraline assessed changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.15 to 0.6). Meta-analysis of two trials involving 113 men with erectile dysfunction found that the addition of sildenafil resulted in less sexual dysfunction at endpoint on rating scales including the International Index of Erectile Function (IIEF) (WMD 19.36, 95% CI 15.00 to 23.72). Another trial found the addition of bupropion led to improved scores on the Changes in Sexual Functioning Questionnaire desire-frequency subscale (WMD 0.88, 95% CI 0.21 to 1.55). In a further study the addition of tadalafil was associated with greater improvement in the erectile function domain of the IIEF than placebo (WMD 8.10; 95% CI 4.62 to 11.68). Other augmentation strategies failed to show statistically significant improvements in sexual dysfunction compared with placebo. DISCUSSION: The currently available evidence is rather limited, with small numbers of trials assessing each strategy. However, while further randomised data is awaited, for men with antidepressant-induced erectile dysfunction, the addition of sildenafil appears to be an effective strategy.
BACKGROUND: Several systematic reviews of school-based smoking prevention trials have shown short-term decreases in smoking prevalence but have not examined long-term follow-up evaluation. The purpose of this study was to conduct a systematic review of rigorously evaluated interventions for school-based smoking prevention with long-term follow-up data. METHODS: We searched online bibliographic databases and reference lists from review articles and selected studies. We included all school-based, randomized, controlled trials of smoking prevention with follow-up evaluation to age 18 or 12th grade and at least 1 year after intervention ended, and that had smoking prevalence as a primary outcome. The primary outcome was current smoking prevalence (defined as at least 1 cigarette in the past month). RESULTS: The abstracts or full-text articles of 177 relevant studies were examined, of which 8 met the selection criteria. The 8 articles included studies differing in intervention intensity, presence of booster sessions, follow-up periods, and attrition rates. Only one study showed decreased smoking prevalence in the intervention group. CONCLUSIONS: Few studies have evaluated the long-term impact of school-based smoking prevention programs rigorously. Among the 8 programs that have follow-up data to age 18 or 12th grade, we found little to no evidence of long-term effectiveness.
PURPOSE: This review systematically examined the relationship between self-esteem and adolescents' sexual behaviors, attitudes, and intentions, as empirically investigated by researchers over the last 20 years. METHODS: Based on the Matrix Method for systematic reviews, five electronic databases and reference lists of published studies were searched. Thirty-eight (n = 38) publications met specific inclusion and exclusion criteria and comprised the final sample. Each study was assigned a methodological quality score (MQS; maximum = 20 points). Each study's empirical test of the relationship between self-esteem and sexual behaviors/attitudes/intentions was counted as a single finding and was classified as exhibiting an inverse linear relationship, no statistically significant linear relationship, or a positive linear relationship. RESULTS: A total of 189 findings (average = 4.97/publication, range 1-28) were analyzed. Most findings (n = 138, 73%) consisted of tests of self-esteem and sexual behaviors. Regarding the nature of the relationship between self-esteem and the various behavior/attitude/intention variables, 62% of behavior findings and 72% of the attitudinal findings exhibited no statistically significant association. All of the intention-related findings exhibited some type of relationship (either positive or inverse). Studies' average MQS was 11.71 (SD = 1.60). Higher quality studies yielded findings of positive or absence of relationship (Cramer's V = .329, p = .001). CONCLUSIONS: If most findings exhibit no association between self-esteem and adolescent sexual behaviors/attitudes/intentions, questions are inevitably raised whether the emphasis placed on self-esteem by public health professionals is innocuous. Recommendations for methodological improvement of this body of research are also presented.
An algorithm is presented for the generation of a reliable peptide component peak table from liquid chromatography-mass spectrometry (LC-MS) and subsequent quantitative analysis of stable isotope coded peptide samples. The method uses chemical noise filtering, charge state fitting, and deisotoping toward improved analysis of complex peptide samples. Overlapping peptide signals in mass spectra were deconvoluted by correlation with modeled peptide isotopic peak profiles. Isotopic peak profiles for peptides were generated in silico from a protein database producing reference model distributions. Doublets of heavy and light labeled peak clusters were identified and compared to provide differential quantification of pairs of stable isotope coded peptides. Algorithms were evaluated using peptides from digests of a single protein and a seven-protein mixture that had been differentially coded with stable isotope labeling agents and mixed in known ratios. The experimental results correlated well with known mixing ratios.
BACKGROUND AND RATIONALE: Sedation can be used to relieve anxiety and manage behaviour in children, unfortunately it is difficult to determine from published research which agents, dosages and techniques are effective. OBJECTIVE: To evaluate the relative efficacy of the various conscious sedation techniques and dosages for behaviour management in paediatric dentistry. DESIGN AND KEY METHODS: Relevant databases and reference lists from articles were searched up to December 2005. Studies were selected if they met the following criteria: randomised controlled trials of conscious sedation comparing two or more drugs/techniques/placebo undertaken by the dentist or one of the dental team in anxious children up to 16 years of age. RESULTS: Sixty-five studies were included with 3372 subjects in total. Overall quality of studies was found to be disappointing with poor reporting often the main problem. CONCLUSIONS: Authors were not able to reach any definitive conclusion on which was the most effective drug or method of sedation used for anxious children due to issues with the quality and validity of published studies to date.
Opioids have been endorsed as appropriate treatment for refractory chronic non-cancer pain when used according to published guidelines. They are widely used for this indication. However, there appear to be gaps in our understanding of the efficacy and safety of individual long-acting opioids compared to each other or as a class compared to short-acting opioids. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of long-acting opioids in the management of chronic non-cancer pain. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included non-parenteral long-acting opioids were sought using electronic databases, handsearching reference lists, and soliciting pharmaceutical company submissions. Searches were performed through October 2002. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 16 randomized trials (comparative efficacy and adverse events), enrolling 1427 patients, and 8 observational studies (adverse events) of 1190 patients were included in this review. No randomized trial was rated good quality; observational studies were generally of poorer quality than the trials. There was insufficient evidence to prove that different long-acting opioids are associated with different efficacy or safety profiles. There was also insufficient evidence to determine whether long-acting opioids as a class are more effective or safer than short-acting opioids. A subgroup of three studies on long-acting versus short-acting oxycodone was more homogeneous and provided fair evidence that these formulations are equally effective for pain control.
BACKGROUND: In femoropopliteal bypass surgery, the use of saphenous vein grafts is preferable, but synthetic grafts are widely used above the knee. The objective of this meta-analysis was to assess the long-term patency of femoropopliteal bypass grafts classified as above-knee polytetrafluoroethylene, above-knee saphenous vein, or below-knee saphenous vein. METHODS: Studies published from 1986 through 2004 were identified from electronic databases and reference lists; 73 articles contributed 1 or more series that used survival analysis, assessed femoropopliteal bypasses in one of the foregoing configurations, reported a 1-year graft patency rate, and included at least 30 bypasses. The series with a predominance of claudicant patients were included in meta-analysis C, and the series in which critical ischemia predominated were included in meta-analysis CI. Pooled survival curves of graft patency were constructed. RESULTS: In meta-analysis C, the pooled primary graft patency was 57.4% for above-knee polytetrafluoroethylene, 77.2% for above-knee vein, and 64.8% for below-knee vein at 5 years; there was a significant difference between above-knee grafts at 3, 4, and 5 years (P < .05). The corresponding pooled secondary graft patency was 73.2%, 80.1%, and 79.7%, respectively (P > .05). In meta-analysis CI, the pooled primary graft patency was 48.3% for above-knee polytetrafluoroethylene, 69.4% for above-knee vein, and 68.9% for below-knee vein at 5 years; there was a significant difference between above-knee grafts until 4 years (P < .05). The corresponding pooled secondary graft patency was 54.0%, 71.9%, and 77.8%, respectively, with a significant difference between above-knee grafts at 2, 3, and 4 years (P < .05). CONCLUSIONS: The great saphenous vein performs better than polytetrafluoroethylene in femoropopliteal bypass grafting and should be used whenever possible.
The problems of identifying environmental factors involved in the etiology of human disease and performing safety and risk assessments of drugs and chemicals have long been formidable issues. Three principal components for predicting potential human health risks are: (1) the diverse structure and properties of thousands of chemicals and other stressors in the environment; (2) the time and dose parameters that define the relationship between exposure and disease; and (3) the genetic diversity of organisms used as surrogates to determine adverse chemical effects. The global techniques evolving from successful genomics efforts are providing new exciting tools with which to address these intractable problems of environmental health and toxicology. In order to exploit the scientific opportunities, the National Institute of Environmental Health Sciences has created the National Center for Toxicogenomics (NCT). The primary mission of the NCT is to use gene expression technology, proteomics and metabolite profiling to create a reference knowledge base that will allow scientists to understand mechanisms of toxicity and to be able to predict the potential toxicity of new chemical entities and drugs. A principal scientific objective underpinning the use of microarray analysis of chemical exposures is to demonstrate the utility of signature profiling of the action of drugs or chemicals and to utilize microarray methodologies to determine biomarkers of exposure and potential adverse effects. The initial approach of the NCT is to utilize proof-of-principle experiments in an effort to "phenotypically anchor" the altered patterns of gene expression to conventional parameters of toxicity and to define dose and time relationships in which the expression of such signature genes may precede the development of overt toxicity. The microarray approach is used in conjunction with proteomic techniques to identify specific proteins that may serve as signature biomarkers. The longer-range goal of these efforts is to develop a reference relational database of chemical effects in biological systems (CEBS) that can be used to define common mechanisms of toxicity, chemical and drug actions, to define cellular pathways of response, injury and, ultimately, disease. In order to implement this strategy, the NCT has created a consortium of research organizations and private sector companies to actively collaborative in populating the database with high quality primary data. The evolution of discrete databases to a knowledge base of toxicogenomics will be accomplished through establishing relational interfaces with other sources of information on the structure and activity of chemicals such as that of the National Toxicology Program (NTP) and with databases annotating gene identity, sequence, and function.
BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy. METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data were abstracted from the various reports to calculate operating characteristics and odds ratios for the different DVH metrics. RESULTS: A total of 12 published studies and two abstracts were identified. Eleven studies assessed V(dose), seven assessed MLD, and eight assessed NTCP. Nine studies exclusively analyzed the association between various DVH metrics and RP risk. Five studies also analyzed other patient, tumor, and treatment variables in conjunction with standard DVH metrics. A direct comparison between studies and the generation of summary statistics (i.e. meta-analysis) could not be achieved due to significant predictive and outcome variable heterogeneity. Most studies did show an association between DVH parameters and RP risk. However, overall accuracy, sensitivity, specificity, and positive predictive value were generally poor to fair for all three classes of DVH metrics. CONCLUSIONS: An association between DVH parameters and RP risk has been demonstrated in the literature. However, the ideal DVH metric with excellent operating characteristics, either alone or in a model with other predictive variables, for RP risk prediction has not yet been identified. Several recommendations for reporting and conduct of future research into the association between DVH metrics and RP risk are provided.
This article describes a systematic literature review on whether, how, and when to perform preoperative hair removal. By searching electronic databases and reference lists of relevant articles, team members identified 20 clinical studies that deal with preoperative hair removal. No strong evidence was found to advocate against preoperative hair removal. Furthermore, there was strong evidence to recommend that when hair removal is considered necessary, shaving should not be performed. Instead a depilatory or electric clipping, preferably immediately before surgery, should be used.
PURPOSE: Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS: We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS: Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (-9 IU/L, 95% CI: -18 to -1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION: Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease.
OBJECTIVE: Our purpose was to analyze published randomized trials assessing the efficacy of maintenance tocolytic therapy after short-term tocolysis in patients with acute preterm labor. STUDY DESIGN: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify randomized trials assessing the efficacy of maintenance tocolytic therapy after resolution of the acute preterm labor episode. Two masked investigators performed independent trial quality evaluation and data abstraction of each trial. We calculated an estimate of the odds ratio and risk difference for dichotomous outcomes, using both a random- and fixed-effects model. Continuous outcomes were pooled with a variance-weighted average of the within-study difference in means. RESULTS: Of 17 studies identified, 12 met our criteria for meta-analysis. These 12 trials included 1590 patients, including 855 who received maintenance tocolysis and 735 comparison patients who received placebo or no maintenance treatment. Compared with placebo or no treatment, the pooled odds ratio for preventing preterm delivery was 0.95 (95% confidence interval, 0. 77-1.17), and the odds ratio for preventing recurrent preterm labor was 0.81 (95% confidence interval, 0.64-1.03). In addition, use of maintenance tocolytic therapy was not associated with decreased rates of neonatal respiratory distress syndrome, perinatal deaths, or differences in birth weight. Although no difference was noted in mean gestational age at delivery, those receiving tocolytic agents had a longer latency period. CONCLUSION: Maintenance tocolytic therapy after successful treatment of an acute episode of preterm labor does not reduce the incidence of recurrent preterm labor or preterm delivery and does not improve perinatal outcome. Accordingly, the results of this meta-analysis do not support the use of maintenance tocolytic therapy after successful treatment of preterm labor.
OBJECTIVE: To systematically review published randomized controlled trials (RCTs) to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify RCTs of misoprostol for cervical ripening and labor induction, which compared repeated doses of 25 microg and 50 microg. STUDY SELECTION: We evaluated, abstracted data, and assessed the quality of RCTs to compare the safety and efficacy of 25 microg versus 50 microg of intravaginal misoprostol for cervical ripening and labor induction. TABULATION, INTEGRATION, AND RESULTS: Five RCTs met inclusion criteria for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome (random- and fixed-effects models). In addition, we aggregated the results of two separate studies, permitting an indirect comparison of the two doses being analyzed. In the meta-analysis, tachysystole and hyperstimulation syndrome appear to occur less frequently among women who received 25 microg of misoprostol than with 50 microg. However, neonatal outcomes appear to be comparable with the two doses. Regarding efficacy, use of the 50-microg dose was associated with a shorter interval to vaginal delivery, greater proportion of deliveries within 24 hours, and less frequent need for oxytocin augmentation. The indirect comparison of two studies yielded similar results. CONCLUSION: Published data indicate that intravaginal misoprostol at doses of 50 microg for cervical ripening and labor induction is more efficacious but it is unclear whether it is as safe as the 25-microg dose.
OBJECTIVE: To provide the obstetrician-gynecologist with the recent advances in mechanisms of chemotherapy resistance in ovarian cancer. DATA SOURCES: A computerized search of articles published through September 1997 was performed on the MEDLINE Ovid and Cancerlit databases. Additional references were identified from the reference section of all selected papers. METHODS OF STUDY SELECTION: All identified references were evaluated as to their relevant contribution to our understanding of the basic mechanisms underlying the response to chemotherapy, the development of chemotherapy resistance in ovarian cancer, and possible strategies for therapy. TABULATION, INTEGRATION, AND RESULTS: One hundred sixteen references were reviewed. A brief summary of the classic concepts on resistance to cisplatin and paclitaxel is provided, followed by a description of the basic mechanisms governing apoptosis and cell cycle arrest as well as their involvement in cell response to chemotherapy and the development of chemoresistance. Finally, a brief summary of the molecular alterations described in ovarian cancer, together with hypothetic strategies for gene-targeted therapy, are reported. CONCLUSION: Cisplatin or paclitaxel chemotherapy induces arrest of the cell cycle or apoptosis in ovarian cancer cells. Tumor suppressor genes such as p53 play a paramount role in mediating this response and p21wAF1/CIP1 is a major mediator of p53-induced arrest of the cell cycle. Molecular alterations involving these tumor suppressor genes are related to the development of resistance to chemotherapy and represent possible targets for gene therapy in ovarian cancer.