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Dan Shen agents for acute ischaemic stroke.

BACKGROUND: Based mainly on experimental data which indicates improvement to the cerebral microcirculation, Dan Shen, a form of herbal medicine, is widely used in the treatment of acute ischaemic stroke in China. We aimed to assess the evidence from randomised controlled trials of their effects. OBJECTIVES: To review the randomised or quasi-randomised controlled trials of Dan Shen agents for acute ischaemic stroke. The primary objective was to determine whether Dan Shen agents improve functional outcome without causing undue harm in patients with acute ischaemic stroke. Secondary objectives were to assess the effect of Dan Shen agents on impairment and on quality of life. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2003), the register of the Cochrane Complementary Field (last searched September 2003) and the Chinese Stroke Trials Register (last searched September 2003). In addition we searched the following bibliographic databases: The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (1996 to December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002), AMED (1985 to December 2002) and China Biological Medicine Database (CBM-disc 1979 to December 2002). We handsearched 10 Chinese journals, searched clinical trials and research databases, scanned reference lists and contacted the pharmaceutical company manufacturing Dan Shen. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing Dan Shen agents with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Eight potentially eligible trials were identified, of which three trials (304 patients) were included. Two trials were excluded and three trials are awaiting assessment. Numbers of deaths and dependent patients at the end of follow-up of at least three months were not reported in the three included trials. Only one trial reported adverse events. Three trials measured the outcome "significant improvement in neurological deficit at the end of treatment". Compound Dan Shen agents were associated with a significant increase in the number of patients with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence Interval (CI) 1.10 to 6.72). No deaths were reported within the first two weeks of treatment or during the whole follow-up period (21 to 28 days). The trials did not include any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were too few patients and outcome events to draw reliable conclusions from the present data. The methodological qualities of all included studies were poor. Further high-quality randomised controlled trials should be performed.

Acute Disease↗

Megestrol acetate for the treatment of anorexia-cachexia syndrome.

BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY: Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002. SELECTION CRITERIA: Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND ANALYSIS: Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.

Acquired Immunodeficiency Syndrome↗

African swine fever virus-induced polypeptides in porcine alveolar macrophages and in Vero cells: two-dimensional gel analysis.

High-resolution two-dimensional electrophoresis followed by computer analysis has been used to study quantitatively the patterns of protein synthesis produced in porcine alveolar macrophages and in Vero cells infected with African swine fever virus (ASFV). Initially, a protein database for each cell type was constructed. The porcine alveolar macrophage database includes 995 polypeptides (818 acidic, isoelectric focusing (IEF) and 177 basic, nonequilibrium pH gradient electrophoresis (NEPHGE)) whereas the Vero database contains 1,398 polypeptides (1,127 acidic, IEF and 271 basic, NEPHGE). Taking these databases as reference, ASFV highly virulent strain E70 induces 57 acid and 43 basic polypeptides in porcine alveolar macrophages, which account for most of the information content of the virus DNA. The kinetics of synthesis of the virus-induced polypeptides showed the existence of three classes of proteins: one whose synthesis starts early after infection, continues for a period and then switches off; another whose synthesis also starts early but continues for prolonged periods; and a third which requires DNA replication. The attenuated, cell adapted, strain BA71V induces 92 acidic and 37 basic proteins in Vero cells. Significant differences were observed when comparing the patterns of polypeptides induced by the two viral strains. In both cell systems studied, ASFV infection produces a general shutoff of protein synthesis that affects up to 65% of the cellular proteins. Interestingly, 28 proteins of porcine alveolar macrophages and 48 proteins of Vero cells are stimulated at least two times by ASFV infection.

African Swine Fever Virus↗

Occurrence of A-waves in F-wave studies of healthy nerves.

A-waves are compound muscle action potentials that follow the M-wave with a constant shape and latency; usually they are detected during F-wave studies. A large reference value database for F-wave parameters from the median, ulnar, peroneal, and tibial nerves was collected from 121-196 subjects aged 14 to 95 years without known pathology involving the studied nerves. From this material, we studied retrospectively the occurrence of A-waves. To be included, an A-wave had to be clearly discriminated from the baseline in at least 8 of 20 traces with a jitter of less than 0.5 ms. A-waves occurred in 25% of the tibial nerves studied and 14% of the peroneal nerves but in only 2% of median and ulnar nerves. In the peroneal and tibial nerves, the frequency of A-waves increased with age, suggesting that A-waves may be related to normal age-related mild neuropathic changes of alpha motor neurons. Thus, A-waves are frequently found in lower-extremity nerves in healthy subjects and less commonly in upper-extremity nerves. Their presence must therefore be interpreted with caution and cannot be taken as necessarily indicative of abnormality.

Adolescent↗

Health promotion in the city: a structured review of the literature on interventions to prevent heart disease, substance abuse, violence and HIV infection in US metropolitan areas, 1980-1995.

To achieve its national public health goals, the US must improve the health of low-income urban populations. To contribute to this process, this study reviewed published reports of health promotion interventions designed to prevent heart disease, HIV infection, substance abuse, and violence in US cities. The study's objectives were to describe the target populations, settings, and program characteristics of these interventions and to assess the extent to which these programs followed accepted principles for health promotion. Investigators searched five computerized databases and references of selected articles for articles published in peer-reviewed journals between 1980 and 1995. Selected articles listed as a main goal primary prevention of one of four index conditions; were carried out within a US city; included sufficient information to characterize the intervention; and organized at least 25% of its activities within a community setting. In general, programs reached a diverse population of low-income city residents in a variety of settings, employed multiple strategies, and recognized at least some of the principles of effective health promotion. Most programs reported a systematic evaluation. However, many programs did not involve participants in planning, intervene to change underlying social causes, last more than a year, or tailor for the subpopulations they targeted, limiting their potential effectiveness. Few programs addressed the unique characteristics of urban communities.

HIV Infections↗

Value of routine preoperative chest x-rays: a meta-analysis.

The purpose of this study was to estimate the frequency with which routine postoperative chest x-rays lead to clinically relevant new information. All articles in English, French and Spanish relating to routine chest radiography in North American or European populations were reviewed, using the Medline database and references listed in reviews and periodicals published from 1966 to 1992, inclusive. Twenty-one reports which supplied sufficient information were included for meta-analysis. On average, abnormalities were found in 10% of routine preoperative chest films. In only 1.3% of films were the abnormalities unexpected, i.e., were not already known or would not otherwise have been detected (95% CI: 0 to 2.8%). These findings were of sufficient importance to cause modification of management in only 0.1% (95% CI: 0 to 0.6%). The frequency with which the new information influenced health could not be estimated. Assuming only the direct cost to the health care system of each radiograph ($23), each finding which influenced management in any way would cost $23,000. It is concluded that in North American or European populations when a reliable history and a clinical examination are carried out, the cost of this test is so high relation to the clinical information provided that it is no longer justifiable.

Age Factors↗

[Minimum requirements in total knee replacement. Evidence report and model calculation of the healthcare situation].

This report assesses the volume-outcome relationship of total knee replacement and the effects of its application on medical care in Germany. Electronic bibliographic databases, the reference lists of relevant articles, and research-related resources of various health services were searched and selected studies were assessed. Additionally, the consequences of implementing a regulation based on volume-outcome relationship were calculated using different models. The results in the literature concerning defined outcome parameters are inconsistent, but in all but one publication a general correlation between high volume and low complication rate could be identified. Implementing a regulation based on volume-outcome relationship with cutoff points of 20/50/100 total knee replacements/year would lead to an exclusion of 242/502/709 hospitals, respectively, from medical care. This would result in a reallocation of 2358 (2.9%)/10752 (13.2%)/25482 (31.2%) patients/year, respectively (extrapolation). The application of a regulation based on volume-outcome considerations in the German healthcare system must be performed very carefully because significant effects are to be expected.

Arthroplasty, Replacement, Knee↗

St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.

RATIONALE: St. John's wort (Hypericum perforatum) has recently gained popularity as an alternative treatment for mild to moderate depression. Given the current widespread use of this herbal remedy, it is important for medical professionals to understand the potential pharmacological pathways through which Hypericum may exert an antidepressant effect. OBJECTIVES: (1) To review the current pharmacological, toxicological, and clinical literature available on Hypericum, and (2) to provide a synthesis of this information into a form that may be easily used by health care providers. METHOD: A comprehensive review of the recent scientific literature (January 1990-March 2000) was performed using the following electronic databases and reference publications: MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all editions), European Scientific Cooperative on Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk Reference for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107) publications in the English language and three publications in German were included in the review. Collectively, the data suggest that therapeutic preparations of Hypericum extract appear to exert potentially significant pharmacological activity within several neurochemical systems believed to be implicated in the pathophysiology of depression. However, little information exists regarding the safety of Hypericum, including potential herb-drug interactions. CONCLUSIONS: Additional research on the pharmacological and biochemical activity of Hypericum and its several bioactive constituents is necessary to further elucidate the mode(s) of antidepressant action. Given what is currently known and unknown about the biological properties of Hypericum, those who choose to use this herb should be closely monitored by a physician.

Animals↗

Species identification by means of pyrosequencing the mitochondrial 12S rRNA gene.

The aim of this study was to develop a new method for species identification based on the analysis of a very short nucleotide sequence. For this reason, the mitochondrial 12S rRNA gene, together with the new method of pyrosequencing, was used. The detection of only 20 nucleotides, following the sequencing primer within a 149-bp fragment by pyrosequencing, was sufficient to identify the biological origin of the samples by alignment with a reference sequence database. A case example with a piece of skin is presented, and the question whether this piece of skin came from a missing wife or from an animal could be answered.

Animals↗

Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations.

The extensive nucleotide diversity in drug-related genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.

Alleles↗

Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome.

OBJECTIVE: To evaluate the accuracy of C-reactive protein (CRP), procalcitonin (PCT), neopterin, and endotoxin in the differential diagnosis of sepsis and non-infectious systemic inflammatory response syndrome (SIRS). METHODS: A Medline database and references from identified articles were used to perform a literature search relating to the differential diagnosis of sepsis versus non-infectious SIRS. RESULTS: CRP, PCT, and neopterin are released both in sepsis and in non-infectious inflammatory disease. CRP and PCT are equally effective, although not perfect, in differentiating between sepsis and non-infectious SIRS. However, CRP and PCT have different kinetics and profiles. The kinetics of CRP is slower than that of PCT, and CRP levels may not further increase during more severe stages of sepsis. On the contrary, PCT rises in proportion to the severity of sepsis and reaches its highest levels in septic shock. PCT tends to be higher in nonsurvivor than in survivor. Therefore, PCT demonstrated a closer correlation with the severity of sepsis and outcome than CRP. Unlike CRP and PCT, neopterin is increased in viral infection as well as bacterial infection, and neopterin is also a useful indicator of sepsis. Endotoxemia was detected in no more than half of patients with Gram-negative bacteremia, and Gram-negative bacteremia was detected in half of patients with endotoxemia. CONCLUSIONS: The diagnostic capacity of PCT is superior to that of CRP due to the close correlation between PCT levels and the severity of sepsis and outcome. Neopterin is very useful in the diagnosis of viral infection. The endotoxin assay in combination with CRP, PCT, or neopterin may help as a diagnostic marker for Gram-negative bacterial infection.

Animals↗

Follow-up by mail in clinical trials: does questionnaire length matter?

In large clinical trials where outcome assessment is possible using questionnaires, it may be more cost-effective to mail them to patients than to conduct interviews in-person. However, nonresponse to mailed questionnaires reduces the effective sample size and can introduce bias. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of questionnaire length on response rates. We searched 14 electronic bibliographic databases, the reference lists of relevant trials, and we contacted the authors of eligible trials to ask about unpublished data. For each trial identified, we used logistic regression to estimate the odds ratio for response per one page increase in the number of pages included in the questionnaire. We pooled the regression coefficients in a random effects meta-analysis. Heterogeneity among the coefficients was assessed using a chi-square test at a 5% significance level. We specified a priori that the reduction in the odds of response per one page increase would be greatest among trials comparing relatively short questionnaires. We used meta regression to examine the relationships between the regression coefficients, the length of the questionnaires used in each trial, and other study characteristics. A total of 38 randomized controlled trials were identified where participants were allocated to questionnaires of differing lengths and where the number of pages used was known. There was significant heterogeneity between the regression coefficients estimated from each trial. In meta regression, most of the heterogeneity was explained by variation in the length of the questionnaires used in each trial. Among trials in which the shortest questionnaire was a postcard, the odds of response were more than halved for each additional page used (0.39; 95% CI 0.34 to 0.45). In the remaining trials, pooled effect sizes were much smaller. In trials of one page compared with either two or three pages, the odds of response per one page increase was 1.01 (95% CI 0.82 to 1.24). For one page compared with four or more pages, and for two or more pages compared with longer alternatives, the odds ratios per one page increase were 0.90 (95% CI 0.83 to 0.98) and 0.98 (95% CI 0.96 to 0.99), respectively. There were no statistically significant associations between trial results and other study characteristics. It appears that response can be increased by using a shorter questionnaire. Moderate changes to the length of shorter questionnaires will be more effective than moderate changes to the length of longer questionnaires. If a choice of follow-up questionnaire exists for a clinical trial, the shorter one should be used. If a new follow-up questionnaire is to be designed, it should be made as short as possible without compromising the data collection requirements of the trial.

Follow-Up Studies↗

Suicidal phenomena and abuse in adolescents: a review of epidemiological studies.

OBJECTIVE: To conduct a systematic review of the international literature to determine whether adolescents who had experienced abuse were more likely to also experience suicidal thoughts and behaviors than other adolescents, and to investigate the nature of this association. METHOD: Reports of community- or school-based studies of adolescents on the association between the prevalence of suicidal phenomena and abuse were searched for via electronic databases, reviewing reference lists and contacting experts in the field. RESULTS: Ten relevant studies were identified. Adolescents who had been physically or sexually abused were significantly more likely to experience suicidal thoughts and behaviors than other adolescents. This association appeared to be direct in most studies in which multivariate analyses were conducted. There is evidence that other factors (e.g., low self-esteem) may play a mediating role in the relationship between abuse and suicidal phenomena. CONCLUSIONS: There is a clear link between abuse and suicidal phenomena occurring during childhood and adolescence.

Adolescent↗

Mapping the oral microbiome opens links to periodontitis.

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.

Humans↗

Australian nurses in general practice based heart failure management: implications for innovative collaborative practice.

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.

Attitude of Health Personnel↗

Androgen replacement therapy in women.

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.

Androgens↗

A systematic review of school-based smoking prevention trials with long-term follow-up.

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.

Adolescent↗

An automated method for the analysis of stable isotope labeling data in proteomics.

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.

Algorithms↗