Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation.

OBJECTIVES: In the UK, colorectal cancer (CRC) is the third most common malignancy (behind lung and breast cancer) with 37,514 cases registered in 2006: around two-thirds (23,384) in the colon and one-third (14,130) in the rectum. Treatment of cancers of the colon can vary considerably, but surgical resection is the mainstay of treatment for curative intent. Following surgical resection, there is a comprehensive assessment of the tumour, it's invasion characteristics and spread (tumour staging). A number of imaging modalities are used in the pre-operative staging of CRCs including; computerised tomography (CT), magnetic resonance imaging, ultrasound imaging and positron emission tomography (PET). This report examines the role of CT in combination with PET scanning (PET/CT 'hybrid' scan). The research objectives are: to evaluate the diagnostic accuracy and therapeutic impact of fluorine-18-deoxyglucose (FDG) PET/CT for the pre-operative staging of primary, recurrent and metastatic cancer using systematic review methods; undertake probabilistic decision-analytic modelling (using Monte Carlo simulation); and conduct a value of information analysis to help inform whether or not there is potential worth in undertaking further research. DATA SOURCES: For each aspect of the research - the systematic review, the handsearch study and the economic evaluation - a database was assembled from a comprehensive search for published and unpublished studies, which included database searches, reference lists search and contact with experts. In the systematic review prospective and retrospective patient series (diagnostic cohort) and randomised controlled trials (RCTs) were eligible for inclusion. Both consecutive series and series that are not explicitly reported as consecutive were included. REVIEW METHODS: Two reviewers extracted all data and applied the criteria independently and resolved disagreements by discussion. Data to populate 2 × 2 contingency tables consisting of the number of true positives, true negatives, false positives and false negatives using the studies' own definitions were extracted, as were data relating to changes in management. Fourteen items from the Quality Assessment of Diagnostic Accuracy Studies checklist were used to assess the methodological quality of the included studies. Patient-level data were used to calculate sensitivity and specificity with confidence intervals (CIs). Data were plotted graphically in forest plots. For the economic evaluation, economic models were designed for each of the disease states: primary, recurrent and metastatic. These were developed and populated based on a variety of information sources (in particular from published data sources) and literature, and in consultation with clinical experts. RESULTS: The review found 30 studies that met the eligibility criteria. Only two small studies evaluated the use of FDG PET/CT in primary CRC, and there is insufficient evidence to support its routine use at this time. The use of FDG PET/CT for the detection of recurrent disease identified data from five retrospective studies from which a pooled sensitivity of 91% (95% CI 0.87% to 0.95%) and specificity of 91% (95% CI 0.85% to 0.95%) were observed. Pooled accuracy data from patients undergoing staging for suspected metastatic disease showed FDG PET/CT to have a pooled sensitivity of 91% (95% CI 87% to 94%) and a specificity of 76% (95% CI 58% to 88%), but the poor quality of the studies means the validity of the data may be compromised by several biases. The separate handsearch study did not yield any additional unique studies relevant to FDG PET/CT. Models for recurrent disease demonstrated an incremental cost-effectiveness ratio of £ 21,409 per quality-adjusted life-year (QALY) for rectal cancer, £ 6189 per QALY for colon cancer and £ 21,434 per QALY for metastatic disease. The value of handsearching to identify studies of less clearly defined or reported diagnostic tests is still to be investigated. CONCLUSIONS: The systematic review found insufficient evidence to support the routine use of FDG PET/CT in primary CRC and only a small amount of evidence supporting its use in the pre-operative staging of recurrent and metastatic CRC, and, although FDG PET/CT was shown to change patient management, the data are divergent and the quality of research is generally poor. The handsearch to identify studies of less clearly defined or reported diagnostic tests did not find additional studies. The primary limitations in the economic evaluations were due to uncertainty and lack of available evidence from the systematic reviews for key parameters in each of the five models. In order to address this, a conservative approach was adopted in choosing DTA estimates for the model parameters. Probabilistic analyses were undertaken for each of the models, incorporating wide levels of uncertainty particularly for the DTA estimates. None of the economic models reported cost-savings, but the approach adopted was conservative in order to determine more reliable results given the lack of current information. The economic evaluations conclude that FDG PET/CT as an add-on imaging device is cost-effective in the pre-operative staging of recurrent colon, recurrent rectal and metastatic disease but not in primary colon or rectal cancers. There would be value in undertaking an RCT with a concurrent economic evaluation to evaluate the therapeutic impact and cost-effectiveness of FDG PET/CT compared with conventional imaging (without PET) for the pre-operative staging of recurrent and metastatic CRC.

Follow-up care for men with prostate cancer and the role of primary care: a systematic review of international guidelines.

The optimal role for primary care in providing follow-up for men with prostate cancer is uncertain. A systematic review of international guidelines was undertaken to help identify key elements of existing models of follow-up care to establish a theoretical basis for evaluating future complex interventions. Many guidelines provide insufficient information to judge the reliability of the recommendations. Although the PSA test remains the cornerstone of follow-up, the diversity of recommendations on the provision of follow-up care reflects the current lack of research evidence on which to base firm conclusions. The review highlights the importance of transparent guideline development procedures and the need for robust primary research to inform future evidence-based models of follow-up care for men with prostate cancer.

Pulse oximetry index: a simple arterial assessment for patients with venous disease.

OBJECTIVE: To provide additional safety data comparing ankle brachial pressure index (ABPI) and pulse oximetry (Lanarkshire Oximetry Index, LOI) as measures of arterial circulation in patients with venous disease of the leg. METHOD: A total of 107 (195 legs) attending hospital leg ulcer clinics participated in this prospective open study. We attempted to measure brachial and foot arterial pressures in all patients using both the handheld Doppler method (ABPI) and pulse oximeter method (LOI). Features of patients with limbs in which either the ABPI or LOI could not be assessed were documented. ABPI and LOI values were compared, and agreement between the two assessment methods was assessed. RESULTS: We found the LOI measurement to be a simpler technique than Doppler ABPI measurement, with an endpoint less prone to the subjective variability associated with the Doppler method. Of the 195 legs assessed,we obtained LOI in 10 in which an ABPI could not be recorded. LOI could not be recorded in only one leg. There was a linear association (p<0.001) and fair agreement (kappa=0.303) between LOI and ABPI in the 184 legs in which both ratios could be measured. There was no evident tendency for LOI to read either low or high compared with ABPI. CONCLUSION: Pulse oximetry LOI is a simple alternative to Doppler ABPI in the screening of patients for arterial disease that could be a contraindication to, or require modification of, compression therapy. It can be measured in some legs that cannot be assessed by Doppler ultrasound.

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria.

BACKGROUND: Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce treatment failure. CQ or AQ plus SP are affordable options of combination treatment, but there is debate about their effectiveness. OBJECTIVES: To assess the combination of CQ or AQ plus SP compared with SP alone for first-line treatment of uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1981 to April 2005), African Index Medicus (1993 to 1998), and reference lists. We also contacted researchers at relevant organizations and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials in adults or children with uncomplicated Plasmodium falciparum malaria were eligible for inclusion. The main outcomes of interest were total and clinical failure at day 28 follow up and serious adverse events. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria. One author extracted data and another checked them independently. We used relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Twelve trials (2107 participants) met the inclusion criteria. A meta-analysis of five AQ trials (461 participants) showed a statistically significant reduction in total failure at day 28 with the combination therapy (RR 0.64, 95% CI 0.46 to 0.91), and meta-analysis of three trials (384 participants) showed a significant reduction in clinical failure at day 28 (RR 0.23, 95% CI 0.11 to 0.49). The statistical significance in the total failure analysis was sensitive to losses to follow up. Data from two CQ trials showed no advantage for total failure with combination therapy at day 28. There was no evidence from the included trials of serious adverse events. AUTHORS' CONCLUSIONS: The evidence base is not strong enough to support firm conclusions. The available evidence suggests that AQ plus SP can achieve less treatment failure than SP, but this might depend on existing levels of parasite resistance to the individual drugs.

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. DATA SOURCES: Electronic databases. Internet resources. Pharmaceutical company submissions. REVIEW METHODS: Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. RESULTS: A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older AEDs or other newer AEDs. For newer AEDs versus placebo, a trend was observed in favour of newer drugs, and there was evidence of statistically significant differences in proportion of responders favouring newer drugs. However, it was not possible to assess long-term effectiveness. Most trials were conducted in patients with partial seizures. For newer AEDs versus older drugs, there was no evidence to assess the effectiveness of LEV, LTG or OXC, and evidence for other newer drugs was limited to single studies. Trials only included patients with partial seizures and follow-up was relatively short. There was no evidence to assess effectiveness of adjunctive LEV, OXC or TPM versus other newer drugs, and there were no time to event or cognitive data. No studies assessed the effectiveness of adjunctive AEDs in the elderly or pregnant women. There was some evidence from one study (GBP versus LTG) that both drugs have some beneficial effect on behaviour in people with learning disabilities. Eighty RCTs reported the incidence of adverse events. There was no consistent or convincing evidence to draw any conclusions concerning relative safety and tolerability of newer AEDs compared with each other, older AEDs or placebo. The integrated economic analysis for monotherapy for newly diagnosed patients with partial seizures showed that older AEDs were more likely to be cost-effective, although there was considerable uncertainty in these results. The integrated analysis suggested that newer AEDs used as adjunctive therapy for refractory patients with partial seizures were more effective and more costly than continuing with existing treatment alone. Combination therapy, involving new AEDs, may be cost-effective at a threshold willingness to pay per quality-adjusted life year (QALY) greater than 20,000 pounds, depending on patients' previous treatment history. There was, again, considerable uncertainty in these results. There were few data available to determine effectiveness of treatments for patients with generalised seizures. LTG and VPA showed similar health benefits when used as monotherapy. VPA was less costly and was likely to be cost-effective. The analysis indicated that TPM might be cost-effective when used as an adjunctive therapy, with an estimated incremental cost-effectiveness ratio of 34,500 pounds compared with continuing current treatment alone. CONCLUSIONS: There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data. Newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a QALY of about 20,000 pounds. There is a need for more direct comparisons of the different AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy. Length of follow-up also needs to be considered. Trials are needed that recruit patients with either partial or generalised seizures; that investigate effectiveness and cost-effectiveness in patients with generalised onset seizures and that investigate effectiveness in specific populations of epilepsy patients, as well as studies evaluating cognitive outcomes to use more stringent testing protocols and to adopt a more consistent approach in assessing outcomes. Further research is also required to assess the quality of life within trials of epilepsy therapy using preference-based measures of outcomes that generate cost-effectiveness data. Future RCTs should use CONSORT guidelines; and observational data to provide information on the use of AEDs in actual practice, including details of treatment sequences and doses.

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria.

BACKGROUND: Amodiaquine and chloroquine give fast relief from malaria symptoms, particularly fever. When used alone in areas where there is some parasite resistance they do not completely clear parasites from the blood in all cases, and so not all patients are cured of infection. The major disadvantage of using sulfadoxine-pyrimethamine alone is that it takes a relatively long time to relieve fever. OBJECTIVES: To assess the effectiveness of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine to treat uncomplicated falciparum malaria. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Science Citation Index, African Index Medicus and LILACS were searched. Experts in the field and drug companies were contacted. SELECTION CRITERIA: Randomised and quasi-randomised trials of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine compared with either drug alone in adults or children with confirmed uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria. Data were extracted by the reviewer and checked independently by another person. MAIN RESULTS: Seven trials were included (1277 patients in total). Fever clearance time was shortened by combination therapy compared to sulfadoxine-pyrimethamine alone. Parasite clearance at day seven follow-up was not significantly different for chloroquine or amodiaquine treatment with or without sulfadoxine-pyrimethamine. Parasite clearance at day 28 was better with combination therapy compared to chloroquine or amodiaquine alone, but not significantly better than sulfadoxine-pyrimethamine alone. There was no evidence from the included trials of serious side effects with combination treatment. REVIEWER'S CONCLUSIONS: In areas where chloroquine or amodiaquine are still effective, despite some degree of resistance, using these drugs in combination with sulfadoxine-pyrimethamine, rather than sulfadoxine-pyrimethamine alone, may make people feel better faster and improve sustained parasites clearance.

Quality of Cochrane reviews: assessment of sample from 1998.

OBJECTIVE: To assess the quality of Cochrane reviews. DESIGN: Ten methodologists affiliated with the Cochrane Collaboration independently examined, in a semistructured way, the quality of reviews first published in 1998. Each review was assessed by two people; if one of them noted any major problems, they agreed on a common assessment. Predominant types of problem were categorised. SETTING: Cyberspace collaboration coordinated from the Nordic Cochrane Centre. STUDIES: All 53 reviews first published in issue 4 of the Cochrane Library in 1998. MAIN OUTCOME MEASURE: Proportion of reviews with various types of major problem. RESULTS: No problems or only minor ones were found in most reviews. Major problems were identified in 15 reviews (29%). The evidence did not fully support the conclusion in nine reviews (17%), the conduct or reporting was unsatisfactory in 12 reviews (23%), and stylistic problems were identified in 12 reviews (23%). The problematic conclusions all gave too favourable a picture of the experimental intervention. CONCLUSIONS: Cochrane reviews have previously been shown to be of higher quality and less biased on average than other systematic reviews, but improvement is always possible. The Cochrane Collaboration has taken steps to improve editorial processes and the quality of its reviews. Meanwhile, the Cochrane Library remains a key source of evidence about the effects of healthcare interventions. Its users should interpret reviews cautiously, particularly those with conclusions favouring experimental interventions and those with many typographical errors.

Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review.

To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon (IFN) vs. IFN alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assessed by the Jadad scale plus allocation concealment. Twenty-two randomized trials (n=1947) were identified. The methodological quality was high in five double-blind trials and low in the 17 remaining trials. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95% CI 1.85-17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and IFN. Phyllanthus species were better than nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus IFN combination on clearance of serum HBeAg (1.56, 1.06-2.32) and HBV DNA (1.52, 1.05-2.21) than IFN alone. No serious adverse event was reported. Based on this review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not strong due to the general low methodological quality and the variations of the herb. Further large trials are needed.

Chinese medicinal herbs for chronic hepatitis B: a systematic review.

AIMS/BACKGROUND: Chronic hepatitis B is a serious health problem worldwide. Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in China and many clinical trials have been conducted. This systematic review is to assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis B. METHODS: Randomised clinical trials comparing Chinese medicinal herbs versus placebo, no intervention, nonspecific treatment, or interferon treatment for chronic hepatitis B with > or = 3 months follow-up were included. No language and blinding limitations were applied. The electronic databases were searched, combined with handsearches on Chinese literature. Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad-scale plus allocation concealment. RESULTS: Nine randomised trials (n=936) were included, with only one being of high quality. There was a funnel plot asymmetry (intercept 3.37, p=0.047). Compared to nonspecific treatment or placebo, the herbal compound Fuzheng Jiedu Tang showed an effect on clearance of serum HBsAg (relative risk 5.19, 95% CI 1.24-21.79), HBeAg (10.85, 3.56-33.06), and HBV DNA (8.50, 1.23-58.85). Polyporus umbellatus polysaccharide showed an effect on serum HBeAg (3.06, 1.13-8.29) and HBV DNA (4.14, 1.0-17.19); Phyllanthus amarus showed an effect on serum HBeAg (3.35, 1.49-7.56). Phyllanthus compound and kurorinone showed no significant difference on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to interferon. No serious adverse event was observed. CONCLUSIONS: Chinese medicinal herbs are not recommended for chronic hepatitis B because of the publication bias and low quality of the trials. Rigorously designed, randomised, double-blind, placebo-controlled trials are needed.

Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus infection.

BACKGROUND: About 350 million people are chronically infected carriers of hepatitis B virus and are at a higher risk of serious illness and death from cirrhosis of the liver and liver cancer. Chinese medicinal herbs have been used widely for more than 2000 years to treat chronic liver disease. OBJECTIVES: To assess whether Chinese medicinal herbs are effective and safe for treating asymptomatic carriers of hepatitis B virus. SEARCH STRATEGY: The trials registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the Cochrane Complementary Medicine Field were searched in combination with MEDLINE, EMBASE, and handsearches of Chinese journals and conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised trials (minimum follow-up three months) in asymptomatic carriers of hepatitis B virus. Chinese medicinal herbs (single herb or compound of herbs) compared with placebo, no intervention, general non-specific treatment, or interferon treatment. Trials of Chinese medicinal herbs plus interferon versus interferon alone were also included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Analysis was performed by intention-to-treat where possible. Pre-specified subgroup analyses were: ethnic origin, age at time of infection, and single herb or compound of herbs. MAIN RESULTS: Three randomised clinical trials (307 patients) that followed patients for three months or more after the end of treatment were included. The methodological quality was poor. The herbal compound 'Jianpi Wenshen recipe' had significant effects on viral markers compared to interferon: relative risk 2.40 (95% CI 1.01 to 5.72) for clearance of serum HBsAg, 2.03 (95% CI 0.98 to 4.20) for clearance of HBeAg, and 2.54 (95% CI 1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomised clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. Data on long-term clinical outcomes and quality of life were lacking. REVIEWER'S CONCLUSIONS: Based on one low quality trial, the medicinal herb 'Jianpi Wenshen recipe' may have an antiviral activity in asymptomatic carriers of hepatitis B virus. However, rigorous randomised, double-blind, placebo-controlled trials are needed before herbs should be used for this condition.

Chinese medicinal herbs for chronic hepatitis B.

BACKGROUND: Hepatitis B virus infection is a serious health problem worldwide. Traditional Chinese medicinal herbs have been widely used to treat chronic liver diseases, and many controlled trials have been done to investigate their efficacy. OBJECTIVES: To assess the efficacy and safety of traditional Chinese medicinal herbs for chronic hepatitis B infection. SEARCH STRATEGY: Searches were applied to the following electronic databases: the CHBG Trials Register, the Cochrane Complementary Medicine Field Trials Register, the Cochrane Library, MEDLINE, EMBASE and BIOSIS. Five Chinese journals and conference proceedings were handsearched. No language restriction was used. SELECTION CRITERIA: Randomised or quasi-randomised trials with at least three months follow-up. Trials of Chinese medicinal herbs (single or compound) compared with placebo, no intervention, general non-specific treatment or interferon treatment were included. Trials of Chinese medicinal herbs plus interferon versus interferon alone were also included. Trials could be double-blind, single-blind or not blinded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. The methodological quality of trials was evaluated using the Jadad-scale plus allocation concealment. Intention-to-treat analyses were performed. MAIN RESULTS: Nine randomised trials, including 936 patients, met the inclusion criteria. Methodological quality was considered adequate in only one trial. There was a significant funnel plot asymmetry (regression coefficient=3.37, standard error 1.40, P=0.047). Ten different medicinal herbs were tested in the nine trials. Compared to non-specific treatment or placebo, Fuzheng Jiedu Tang (compound of herbs) showed significantly positive effects on clearance of serum HBsAg, HBeAg, and HBV DNA; Polyporus umbellatus polysaccharide on serum HBeAg and HBV DNA; Phyllanthus amarus on serum HBeAg. Phyllanthus compound and kurorinone showed no significant effect on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to interferon treatment. There were no significant effects of the other examined herbs. REVIEWER'S CONCLUSIONS: Some Chinese medicinal herbs may work in chronic hepatitis B. However, the evidence is too weak to recommend any single herb. Rigorously designed, randomised, double-blind, placebo-controlled trials are required.

Case-controlled study of nursing home residents referred for treatment of vocally disruptive behavior.

The aim of this study was to identify factors associated with vocally disruptive behavior (VDB) in nursing home patients referred to aged care services for treatment, using a case-control methodology. Characteristics of the VDB, reasons for referral, perceived causal factors, and psychotropic use were noted. Twenty-five subjects and controls were examined with the Screaming Behavior Mapping Instrument, the Cornell Scale for Depression in Dementia, the Dementia Behavior Disturbance Scale, and measures of cognition, functional capacity, social activities, and emotional reactions of nursing staff. VDB was associated with other disturbed behaviors, depression, anxiety, severe dementia, functional impairment, communication difficulties, use of psychotropic medication, social isolation, and emotional distress in the nursing staff. Reasons for referral may relate more to the stress experienced by nursing home staff in managing VDB than to specific attributes of the VDB itself.

Cannabinoid receptors on goldfish retinal bipolar cells: electron-microscope immunocytochemistry and whole-cell recordings.

Cannabinoid CB1 receptors are distributed throughout the CNS and interact with GABA, glutamate, and dopamine systems. Cannabinoids have effects on the visual system, some of which may have a retinal component, particularly the enhancement of photosensitivity. We used immunocytochemistry and whole-cell recording to study cannabinoids in the goldfish retina. Immunoblots of an antiserum against amino acids (1-14) of the rat CB1 receptor produced a single band in goldfish retina at about 70 kDa. Light microscope immunocytochemistry of CB1 receptor immunoreactivity (CB1R-IR) revealed intense staining of Müller cells and weaker staining of ON bipolar cells (verified with double labeling with PKC-IR) and the outer and inner plexiform layers. Ultrastructural analysis revealed that CB1R-IR was localized intracellularly as well as on the plasma membrane of photoreceptor terminals, bipolar cell terminals and, rarely, amacrine cell boutons. Membrane-associated CB1R-IR was restricted to cone pedicles at sites removed from the synaptic ribbon. Regarding bipolar cells, membrane-associated CB1R-IR was found at 93% of the synaptic terminals in sublamina b (ON-type) and only at 33% of the synaptic terminals in sublamina a (OFF-type). Whole-cell recordings from large ON-type Mb bipolar cells showed that the delayed rectifier (I(K(V))) was rapidly and reversibly inhibited by 1 microM of the cannabinoid agonists CP 54490 and (+)-WIN 55212-2, effects blocked completely by the antagonist SR 141716A (1 microM). Inhibition of I(K(V)) in the Mb bipolar cells by cannabinoids should result in a more tonic ON response to increments of light. As such, cannabinoids may play a role in modulating the temporal aspects of signaling in the retina.

Artemisinin derivatives for treating uncomplicated malaria.

BACKGROUND: Artemisinin derivatives are a relatively new group of drugs with antimalarial properties. As resistance to other antimalarial drugs continues to increase, artemisinin drugs may be useful alternatives. OBJECTIVES: The objective of this review was to assess the effects of artemisinin drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Science Citation Index, Lilacs, African Index Medicus; conference abstracts and reference lists of relevant articles. We contacted organisations, researchers in the field and drug companies. SELECTION CRITERIA: Randomised and quasi-randomised trials of artemisinin derivatives, alone or in combination with other antimalarials, compared with standard antimalarial treatments, in adults or children with uncomplicated falciparum malaria. Only trials where treatment was given by mouth or suppository were included. Comparisons between different artemisinin derivatives and treatment regimens were also included. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed and data were extracted independently by the two reviewers. MAIN RESULTS: Forty-one trials involving over 5000 patients were included. Variation in study design and quality made synthesis of the data problematic. Allocation concealment was adequate in only two trials. Most data were from areas of multidrug resistant falciparum malaria in South East Asia. Compared with standard antimalarial treatments, artemisinin drugs showed fast parasite clearance and high cure rates at follow-up, provided the duration of treatment with artemisinin drugs was adequate. Combination with mefloquine improved sustained parasite clearance and was effective in multidrug resistant areas. When doses were adequate, the combination shortened the duration of treatment. We found no evidence that artemisinin drugs are more harmful than standard treatment drugs over a typical trial period of 28 days. REVIEWER'S CONCLUSIONS: The evidence suggests that artemisinin drugs are effective and safe for treating uncomplicated malaria. There is no evidence from randomised trials that one artemisinin derivative is better than the others. In areas where there is mefloquine resistance, combination therapy with an artemisinin derivative appears to improve sustained parasite clearance compared with either drug alone.

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria.

BACKGROUND: Amodiaquine and chloroquine give fast relief from malaria symptoms, particularly fever. When used alone in areas where there is some parasite resistance they do not completely clear parasites from the blood in all cases, and so not all patients are cured of infection. The major disadvantage of using sulfadoxine-pyrimethamine alone is that it takes a relatively long time to relieve fever. OBJECTIVES: To assess the effectiveness of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine to treat uncomplicated falciparum malaria. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Science Citation Index, African Index Medicus and LILACS were searched. Experts in the field and drug companies were contacted. SELECTION CRITERIA: Randomised and quasi-randomised trials of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine compared with either drug alone in adults or children with confirmed uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria. Data were extracted by the reviewer and checked independently by another person. MAIN RESULTS: Five trials were included. Fever clearance time was reduced by combination therapy compared with sulfadoxine-pyrimethamine alone. Parasite clearance at day seven follow-up was not significantly different for chloroquine or amodiaquine treatment with or without sulfadoxine-pyrimethamine. Parasite clearance at day 28 was better with combination therapy compared with chloroquine or amodiaquine alone (odds ratio 14.28, 95% confidence interval 6.76 to 30.19), but not significantly better than sulfadoxine-pyrimethamine alone (odds ratio 3.17, 95% confidence interval 0.96 to 10.43). There was no evidence from the included trials of serious side effects with combination treatment. REVIEWER'S CONCLUSIONS: In areas where chloroquine or amodiaquine are still effective, despite some degree of resistance, using these drugs in combination with sulfadoxine-pyrimethamine, rather than sulfadoxine-pyrimethamine alone, may make people feel better faster and improve sustained parasites clearance.

Artemisinin derivatives for treating severe malaria.

BACKGROUND: Artemisinin derivatives may have advantages over quinoline drugs for treating severe malaria since they are fast acting and effective against quinine resistant malaria parasites. OBJECTIVES: The objective of this review was to assess the effects of artemisinin drugs for severe and complicated falciparum malaria in adults and children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, Cochrane Controlled Trials Register, Medline, Embase, Science Citation Index, Lilacs, African Index Medicus, conference abstracts and reference lists of articles. We contacted organisations, researchers in the field and drug companies. SELECTION CRITERIA: Randomised and pseudo-randomised trials comparing artemisinin drugs (rectal, intramuscular or intravenous) with standard treatment, or comparisons between artemisinin derivatives in adults or children with severe or complicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Twenty three trials are included, allocation concealment was adequate in nine. Sixteen trials compared artemisinin drugs with quinine in 2653 patients. Artemisinin drugs were associated with better survival (mortality odds ratio 0.61, 95% confidence interval 0.46 to 0.82, random effects model). In trials where concealment of allocation was adequate (2261 patients), this was barely statistically significant (odds ratio 0.72, 95% CI 0.54 to 0.96, random effects model). In 1939 patients with cerebral malaria, mortality was also lower with artemisinin drugs overall (odds ratio 0.63, 95% CI 0.44 to 0.88, random effects model). The difference was not significant however when only trials reporting adequate concealment of allocation were analysed (odds ratio 0.78, 95% CI 0.55 to 1.10, random effects model) based on 1607 patients. No difference in neurological sequelae was shown. Compared with quinine, artemisinin drugs showed faster parasite clearance from the blood and similar adverse effects. REVIEWER'S CONCLUSIONS: The evidence suggests that artemisinin drugs are no worse than quinine in preventing death in severe or complicated malaria. No artemisinin derivative appears to be better than the others.