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PubMed2006

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel.

BACKGROUND: Tumor promoters enhance tumor yield in experimental animals without directly affecting the DNA of the cell. Promoters may play a role in the development of cancer, as humans are exposed to them in the environment. In work based on computer-assisted microscopy and sophisticated classification methods, we showed that cells could be classified by reference to a database of known normal and cancerous cell phenotypes. Promoters caused loss of properties specific to normal cells and gain of properties of cancer cells. Other compounds, including colchicine, had a similar effect. Colchicine given together with paclitaxel, however, caused cells to adopt properties of normal cells. This provided a rationale for tests of microtubule inhibitor combinations in cancer patients. The combination of a depolymerizing and a stabilizing agent is a superior anti-tumor treatment. The biological basis of the effect is not understood. RESULTS: A single compound containing both colchicine and paclitaxel structures was synthesized. Colchicine is an alkaloid with a trimethoxyphenyl ring (ring A), a ring with an acetamide linkage (ring B), and a tropolone ring (ring C). Although rings A and C are important for tubulin-binding activity, the acetamide linkage on ring B could be replaced by an amide containing a glutamate linker. Alteration of the C-7 site on paclitaxel similarly had little or no inhibitory effect on its biological activity. The linker was attached to this position. The coupled compound, colchitaxel (1), had some of the same effects on microtubules as the combination of starting compounds. It also caused shortening and fragmentation of the + end protein cap. CONCLUSION: Since microtubule inhibitor combinations give results unlike those obtained with either inhibitor alone, it is important to determine how such combinations affect cell shape and growth. Colchitaxel shows a subset of the effects of the inhibitor combination. Thus, it may be able to bind the relevant cellular target of the combination. It will be useful to determine the basis of the shape reversal effect and possibly, the reasons for therapeutic efficacy of microtubule inhibitor combinations.

Journal Article↗

PubMed2007

DiscoverySpace: an interactive data analysis application.

DiscoverySpace is a graphical application for bioinformatics data analysis. Users can seamlessly traverse references between biological databases and draw together annotations in an intuitive tabular interface. Datasets can be compared using a suite of novel tools to aid in the identification of significant patterns. DiscoverySpace is of broad utility and its particular strength is in the analysis of serial analysis of gene expression (SAGE) data. The application is freely available online.

Animals↗

PubMed2004

Systematic review of bisphosphonates for hypercalcaemia of malignancy.

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.

Diphosphonates↗

PubMed2005

Meta-review of high-quality systematic reviews of interventions in key areas of liaison psychiatry.

BACKGROUND: When planning and delivering a liaison psychiatry service it is important to have an understanding of the research evidence supporting the use of interventions likely to be delivered by the service. AIMS: To identify high-quality systematic reviews for all interventions in three defined areas of liaison psychiatry, to summarise their clinical implications and to highlight areas where more research is needed. The three areas were the psychological effects of physical illness or treatment, somatoform disorders and self-harming behaviour. METHOD: Computerised database searching, secondary reference searching, hand-searching and expert consultation were used to identify relevant systematic reviews. Studies were reliably selected, and quality-assessed, and data were extracted and interpreted by two reviewers. RESULTS: We found 64 high-quality systematic reviews. Only 14 reviews included meta-analyses. CONCLUSIONS: Many areas of liaison psychiatry practice are not based on high-quality evidence. More research in this area would help inform development and planning of liaison psychiatry services.

Disease↗

PubMed2003

Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the evidence regarding antiepileptic drug (AED) prophylaxis in patients with severe traumatic brain injury (TBI) in order to make practice recommendations. METHODS: The authors identified relevant studies by searching multiple databases and reviewing reference lists of other sources. They included studies that prospectively compared post-traumatic seizure rates in patients given AED prophylaxis vs controls. Each study was graded (class I to IV) according to a standard classification-of-evidence scheme and results were analyzed and pooled. RESULTS: Pooled class I studies demonstrated a significantly lower risk of early post-traumatic seizures (those occurring within 7 days after injury) in patients given phenytoin prophylaxis compared to controls (relative risk 0.37, 95% CI 0.18 to 0.74). Pooled class I and class II studies demonstrated no significant difference in the risk of late post-traumatic seizures (those occurring beyond 7 days after injury) in patients given AED prophylaxis compared to controls (relative risk 1.05, 95% CI 0.82 to 1.35). Serum AED levels were suboptimal in these studies and adverse effects were mild but frequent. CONCLUSIONS: For adult patients with severe TBI, prophylaxis with phenytoin is effective in decreasing the risk of early post-traumatic seizures. AED prophylaxis is probably not effective in decreasing the risk of late post-traumatic seizures. Further studies addressing milder forms of TBI, the use of newer AEDs, the utility of EEG, and the applicability of these findings to children are recommended.

Acute Disease↗

PubMed2006

The role of specific 2'-hydroxyl groups in the stabilization of the folded conformation of kink-turn RNA.

The role of 2'-hydroxyl groups in stabilizing the tightly kinked geometry of the kink-turn (K-turn) has been investigated. Individual 2'-OH groups have been removed by chemical synthesis, and the kinking of the RNA has been studied by gel electrophoresis and fluorescence resonance energy transfer. The results have been analyzed by reference to a database of 11 different crystallographic structures of K-turns. The potential hydrogen bonds fall into several classes. The most important are those in the core of the turn and ribose-phosphate interactions around the bulge. Of these the single most important hydrogen bond is one donated from the 2'-OH of the 5' nucleotide of the bulge to the N1 of the adenine of the kink-proximal A*G pair. This is present in all known K-turn structures, and removal of the 2'-OH completely prevents metal ion-induced folding. Hydrogen bonds formed in the minor grooves of the helical stems are less important, and removal of the participating 2'-OH groups leads to reduced impairment of folding. These interactions are generally more polymorphic, and hydrogen bonds probably form where possible, as permitted by the global structure.

Archaeoglobus fulgidus↗

PubMed2005

Hyoscine vs glycopyrronium for drying respiratory secretions in dying patients.

The 'death rattle' is a common symptom among dying people, and causes a great deal of anxiety and upset to relatives and carers, including nurses. A mini-review was carried out to evaluate the effectiveness of two drugs--hyoscine hydrobromide and glycopyrronium--in drying up respiratory secretions in terminally ill patients. Searches were made of the Cochrane Library, Medline, Embase, Cinahl and Pharmline. Reference lists, trial databases and professional colleagues were also consulted. There was a scarcity of research material directly comparing the effects of the two drugs in the clinical setting. Two papers were used for comparison in the review but these produced conflicting results. Many discrepancies existed in terms of research methods, and in results. One paper demonstrated that hyoscine hydrobromide was the more effective drug; the other favoured glycopyrronium. There is no clear evidence to support the choice of one drug over the other, based on the clinical outcome selected for this review. Although clinical trials are difficult to conduct in this vulnerable patient group, more research is needed to facilitate the best management of this distressing symptom and allow clinical guidelines to be produced.

Dose-Response Relationship, Drug↗

PubMed2001

Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression.

OBJECTIVE: To compare the benefits and risks of bupropion and selective serotonin-reuptake inhibitors (SSRIs) in adults with depression. DATA SOURCES: MEDLINE (1966-September 1999), Embase (1980-August 1999), PsyclNFO (1887-August 1999), International Pharmaceutical Abstracts (1970-August 1999), and CIANHL databases were searched. References from the selected citations, review articles, and the manufacturer were also screened. STUDY SELECTION: Included studies were randomized, double-blind, controlled trials evaluating bupropion versus SSRIs for depression in adults. Studies were assessed independently in duplicate. Discrepancies were resolved by consensus. DATA ANALYSIS: Data are reported as absolute weighted mean differences or relative risks and 95% confidence intervals comparing bupropion relative to SSRIs. Data not combined are presented qualitatively. DATA SYNTHESIS: Six full-length studies were included of 257 citations identified. SSRI comparators were fluoxetine, sertraline, and paroxetine. No differences in Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions Scale for Improvement of illness (CGI-I) were found, but data were not able to be quantitatively combined. The absolute weighted mean differences were 0.10 (95% CI -0.2 to 0.4) for the CGI for Severity of Illness and 0.37 (95% CI -0.85 to 1.6) for the Hamilton Rating Scale for Anxiety measurements. Relative risks of bupropion compared with SSRIs were 0.6 (95% CI 0.41 to 0.89), 0.31 (95% CI 0.16 to 0.57), and 0.27 (95% CI 0.15 to 0.48) for nausea, diarrhea, and somnolence, respectively. Sexual arousal disorder, orgasmic dysfunction, and sexual desire disorder occurred less with bupropion than with SSRIs, with relative risks of 0.46 (95% CI 0.26 to 0.83), 0.22 (95% CI 0.12 to 0.40), and 0.65 (95% CI 0.51 to 0.84), respectively. CONCLUSIONS: Bupropion and SSRIs have similar effectiveness; however, bupropion was associated with less nausea, diarrhea, somnolence, and sexual dysfunction.

Adult↗

PubMed2006

Does random treatment assignment cause harm to research participants?

BACKGROUND: Some argue that by precluding individualized treatment, randomized clinical trials (RCTs) provide substandard medical care, while others claim that participation in clinical research is associated with improved patient outcomes. However, there are few data to assess the impact of random treatment assignment on RCT participants. We therefore performed a systematic review to quantify the differences in health outcomes between randomized trial participants and eligible non-participants. METHODS AND FINDINGS: Studies were identified by searching Medline, the Web of Science citation database, and manuscript references. Studies were eligible if they documented baseline characteristics and clinical outcomes of RCT participants and eligible non-participants, and allowed non-participants access to the same interventions available to trial participants. Primary study outcomes according to patient group (randomized trial participants versus eligible non-participants) were extracted from all eligible manuscripts. For 22 of the 25 studies (88%) meeting eligibility criteria, there were no significant differences in clinical outcomes between patients who received random assignment of treatment (RCT participants) and those who received individualized treatment assignment (eligible non-participants). In addition, there was no relation between random treatment assignment and clinical outcome in 15 of the 17 studies (88%) in which randomized and nonrandomized patients had similar health status at baseline. CONCLUSIONS: These findings suggest that randomized treatment assignment as part of a clinical trial does not harm research participants.

Cardiology↗

PubMed1999

Corticosteroids in the emergency department therapy of acute adult asthma: an evidence-based evaluation.

OBJECTIVE: To review the literature to determine the benefits of corticosteroids (CCSs) (oral, IM, IV, or inhaled) in the treatment of adult patients with acute asthma presenting at an acute-care setting. SEARCH STRATEGY: A MEDLINE search was conducted using the following terms: (1) Asthma OR Wheez, AND (2) Glucocorticoids OR Steroids, AND (3) Acute OR Emerg. Other sources were the CURRENT CONTENTS database, review articles, reference sections of located studies, and a manual search of the top 15 journals for respiratory and emergency medicine. SELECTION CRITERIA: Patients were selected for the study by the following criteria: (1) English language; (2) adult patients with asthma whose acute exacerbations were the primary reason for assessment; (3) involvement in randomized, controlled trials conducted in an emergency care setting; (4) patients had participated in a study investigating a primary research question involving treatment with CCSs; and (5) outcomes based on results of pulmonary function tests and on hospital admission rates. RESULTS: At the 3-h assessment, only high doses of inhaled CCSs significantly improved pulmonary function compared with placebo (effect size [ES], 0.56; 95% confidence interval [CI], 0.15 to 0.97). On the other hand, after receiving IV CCSs, patients required at least 6 to 24 h to show moderate but nonsignificant improvements of pulmonary function (6-h ES, 0.44 [95% CI, -0.01 to 0.89]; 12-h ES, 0.54 [95% CI, -0.08 to 1.17]; and 24-h ES, 0.53 [95% CI, -0.39 to 1.45]). The data from the six studies that we used to pool information on admission rate outcome showed a 32% reduction in favor of the use of IV CCSs (relative risk [RR], 0.68 [95% CI, 0.47 to 0.99]; number needed to treat, 12.5 [95% CI, 7.1 to 50]). However, the pooled effect of the three high-quality studies showed no difference between groups (RR, 1.21; 95% CI, 0.67 to 2.18). Oral CCSs provided a similarly beneficial effect on pulmonary function when compared with parenteral administration (ES, -0.14; 95% CI, -0.82 to 0.31. Finally, the results showed a nonsignificant favorable trend toward improved outcome with medium or high doses of CCSs. CONCLUSIONS: This evidence-based evaluation suggests that the administration of parenteral CCSs to the patient on arrival at the emergency department (ED) neither improves airflow obstruction nor reduces the need for hospitalization. Parenteral CCSs probably require >6 to 24 h to begin to act. Comprehensible conclusions about admission rates in the ED setting are difficult to make. At the 3-h assessment, only high doses of inhaled CCSs (in one study) significantly improved pulmonary function compared with placebo. IV and oral CCSs appear to have equivalent effects, and there is a tendency toward improvement in pulmonary function with medium or high doses.

Adult↗

PubMed2006

Quality of life in patients with benign thyroid disorders. A review.

The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.

Graves Ophthalmopathy↗

PubMed2006

Lasers in periodontics: a review of the literature.

BACKGROUND: Despite the large number of publications, there is still controversy among clinicians regarding the application of dental lasers to the treatment of chronic periodontitis. The purpose of this review is to analyze the peer-reviewed research literature to determine the state of the science concerning the application of lasers to common oral soft tissue problems, root surface detoxification, and the treatment of chronic periodontitis. METHODS: A comprehensive computer-based search combined the following databases into one search: Medline, Current Contents, and the Cumulated Index of Nursing and Allied Health. This search also used key words. In addition, hand searches were done for several journals not cataloged in the databases, and the reference lists from published articles were checked. All articles were considered individually to eliminate non-peer-reviewed articles, those dealing with commercial laser technology, and those considered by the author to be purely opinion articles, leaving 278 possible articles. RESULTS: There is a considerable conflict in results for both laboratory studies and clinical trials, even when using the same laser wavelength. A meaningful comparison between various clinical studies or between laser and conventional therapy is difficult at best and likely impossible at the present. Reasons for this dilemma are several, such as different laser wavelengths; wide variations in laser parameters; insufficient reporting of parameters that, in turn, does not allow calculation of energy density; differences in experimental design, lack of proper controls, and differences in severity of disease and treatment protocols; and measurement of different clinical endpoints. CONCLUSIONS: Based on this review of the literature, there is a great need to develop an evidence-based approach to the use of lasers for the treatment of chronic periodontitis. Simply put, there is insufficient evidence to suggest that any specific wavelength of laser is superior to the traditional modalities of therapy. Current evidence does suggest that use of the Nd:YAG or Er:YAG wavelengths for treatment of chronic periodontitis may be equivalent to scaling and root planing (SRP) with respect to reduction in probing depth and subgingival bacterial populations. However, if gain in clinical attachment level is considered the gold standard for non-surgical periodontal therapy, then the evidence supporting laser-mediated periodontal treatment over traditional therapy is minimal at best. Lastly, there is limited evidence suggesting that lasers used in an adjunctive capacity to SRP may provide some additional benefit.

Chronic Disease↗

PubMed2003

Colles fracture, spine fracture, and subsequent risk of hip fracture in men and women. A meta-analysis.

BACKGROUND: In postmenopausal women, a history of any fracture is an important risk factor for a future hip fracture. Whether similar findings apply to aging men remains to be established. We conducted a systematic review and meta-analysis of the literature to compare men and women with respect to the relative risk of hip fracture after a wrist or spine fracture. METHODS: Studies published in full from January 1982 through September 2002 in English, French, or German were identified from the PubMed database and from reference lists of retrieved articles. We included cohort studies that reported fractures associated with minimal trauma of the wrist or spine as a risk factor for a subsequent hip fracture among (white) women and men who were fifty years old or older. Data were extracted by two independent reviewers and were checked for accuracy in a second review. Differences in assessments were resolved by consensus of the two reviewers. RESULTS: Nine cohort studies were included in this meta-analysis: five studies were conducted in the United States and four, in Europe. After homogeneity of association was demonstrated across all studies, a fixed-effects meta-analysis was used to calculate pooled relative risks with 95% confidence intervals. Among postmenopausal women, the relative risks for a future fracture of the hip after a fracture of the wrist or spine were 1.53 (95% confidence interval, 1.34 to 1.74; p < 0.001) and 2.20 (95% confidence interval, 1.92 to 2.51; p < 0.001), respectively. In older men, these relative risks were 3.26 (95% confidence interval, 2.08 to 5.11; p < 0.001) and 3.54 (95% confidence interval, 2.01 to 6.23; p < 0.001), respectively. Fractures of the distal part of the radius increased the relative risk of hip fracture significantly more in men than in women (p = 0.002). The impact of a spine fracture, conversely, did not differ between genders (p = 0.11). Sensitivity analyses with use of random-effects methodology confirmed these findings to be robust. CONCLUSIONS: This meta-analysis suggests that a previous spine fracture has an equally important impact on the risk of a subsequent hip fracture in both genders. The prospective association between a Colles fracture and a subsequent hip fracture, however, is significantly stronger among men than among postmenopausal women. Men with a Colles fracture are at high risk for a future hip fracture and should be evaluated as candidates for preventive measures.

Age Factors↗

PubMed2006

Diabetes and impaired fasting glucose as predictors of morbidity and mortality in male coronary artery disease patients with reduced left ventricular function.

OBJECTIVES: To evaluate the prognostic value of impaired fasting glucose and diabetes mellitus in male patients with coronary artery disease and poor left ventricular function. METHODS AND RESULTS: From a prospective database on patients referred for gated myocardial perfusion imaging between 1998 and 2002 all male patients with a history of coronary artery disease and poor left ventricular function were selected. Poor function was defined as left ventricular ejection fraction < or = 40%. Subjects were classified as non-diabetics with fasting blood glucose levels < 110 mg/dL, non-diabetics with impaired fasting glucose (fasting blood glucose between 110 and 125 mg/dL) and diabetics. Median follow-up was 2.7years. End points were all-cause mortality, cardiac death and hospitalization for heart failure. One hundred and sixty patients were selected (age 65 +/- 9 years and left ventricular ejection fraction 29 +/- 8%). In univariate analysis atrial fibrillation, NYHA class, glycaemia and diabetes mellitus discriminated between survivors and non-survivors. In Cox multivariate regression analysis for all-cause mortality only NYHA class and diabetes mellitus remained significant. Kaplan Meier analysis showed that diabetics had the worst survival and non-diabetics with glucose < 110 mg/dL had the best survival. Non-diabetics with impaired fasting glucose had intermediate survival. Analysis for cardiac death/hospitalization for heart failure showed similar results. CONCLUSION: In male patients with coronary artery disease and impaired left ventricular function diabetes mellitus and fasting glucose are strongly predictive of poor outcome. Diabetics have the worst prognosis but non-diabetics with impaired fasting glucose also are at higher risk compared to nondiabetics with low fasting blood glucose.

Aged↗

PubMed2002

Loader Lite: a new software tool for the ABI PRISM 3700 DNA sequencer.

Here we describe the development of a novel software tool entitled Loader Lite that generates plate records or sample sheetsfor the ABI PRISMs 3700 DNA sequencer. The major advantage of this program is that it enables the ongoing operation of sequencing instruments without reference to external network(s). The autonomous operation of sequencing instruments is critical if sample throughput is to be maintained during periods of network outage. Loader Lite employs a deliberate strategy of inputting anonymous tray barcodes at run time. After sequencing, the barcodes are reconciled with relevant project details by reference to a database. This software takes advantage of barcode scanning technology by creating plate records directly on the local computer, serving an individual sequencer, immediately before importing and linking. This real-time synthesis of the plate records at the point of loading all but eliminates loading errors. Loader Lite is user-friendly, fully configurable, and permits the running of partial or full 384-well sample trays, using any standard combinations of run modules, dye sets, mobility files, analysis modules, etc. The 96-well format is not supported; however, this capability will appear in subsequent versions that are currently under development. This application is designed as an added value, adjunct program to the regular ABI PRISM 3700 Data Collection software. We have successfully used Loader Lite over the past six months to load approximately 7 million sequencing reactions and believe its utility and functionality will prove to be attractive to the wider sequencing community.

Sequence Analysis, DNA↗

PubMed2002

A systematic review of the safety of kava extract in the treatment of anxiety.

This paper systematically reviews the clinical evidence relating to the safety of extracts of the herbal anxiolytic kava (Piper methysticum). Literature searches were conducted in four electronic databases and the reference lists of all papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting schemes of the WHO and national drug safety bodies and ten manufacturers of kava preparations were contacted. Data from short-term post-marketing surveillance studies and clinical trials suggest that adverse events are, in general, rare, mild and reversible. However, published case reports indicate that serious adverse events are possible including dermatological reactions, neurological complications and, of greatest concern, liver damage. Spontaneous reporting schemes also suggest that the most common adverse events are mild, but that serious ones occur. Controlled trials suggest that kava extracts do not impair cognitive performance and vigilance or potentiate the effects of central nervous system depressants. However, a possible interaction with benzodiazepines has been reported. It is concluded that when taken as a short-term monotherapy at recommended doses, kava extracts appear to be well tolerated by most users. Serious adverse events have been reported and further research is required to determine the nature and frequency of such events.

Anti-Anxiety Agents↗

PubMed2005

The safety of herbal medicinal products derived from Echinacea species: a systematic review.

Echinacea spp. are native to North America and were traditionally used by the Indian tribes for a variety of ailments, including mouth sores, colds and snake-bites. The three most commonly used Echinacea spp. are E. angustifolia, E. pallida and E. purpurea. Systematic literature searches were conducted in six electronic databases and the reference lists of all of the papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting programmes of the WHO and national drug safety bodies. Twenty-three manufacturers of echinacea were contacted and asked for data held on file. Finally our own departmental files were searched. No language restrictions were imposed. Combination products and homeopathic preparations were excluded. Data from clinical studies and spontaneous reporting programmes suggest that adverse events with echinacea are not commonly reported. Gastrointestinal upsets and rashes occur most frequently. However, in rare cases, echinacea can be associated with allergic reactions that may be severe. Although there is a large amount of data that investigates the efficacy of echinacea, safety issues and the monitoring of adverse events have not been focused on. Short-term use of echinacea is associated with a relatively good safety profile, with a slight risk of transient, reversible, adverse events. The association of echinacea with allergic reactions is supported by the present evaluation. While these reactions are likely to be rare, patients with allergy or asthma should carefully consider their use of echinacea. The use of echinacea products during pregnancy and lactation would appear to be ill-advised in light of the paucity of data in this area.

Adult↗

PubMed2003

Frequency of hospitalisations and inpatient care costs of manic episodes: in patients with bipolar I disorder in France.

BACKGROUND: Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment. However, very few recent studies have investigated the economic burden of the disease. OBJECTIVE: To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France. METHOD: A cost-of-illness study was conducted based on available data using a hospital payer perspective. The lifetime prevalence of manic episodes was estimated from published epidemiological data using a random-effects meta-analysis. Data were obtained by a computerised literature search using the main scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital. Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris, France for the year 1999. RESULTS: Extrapolating from international data on the average prevalence of bipolar I disorder, the proportion of rapid cycling patients and the average cycle duration, we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265,000 in France. Based on hospital data in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63%. The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs (Euro 3 billion) [1999 values]. CONCLUSION: Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. As the lifetime prevalence of bipolar I disorder may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France.

Bipolar Disorder↗