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.

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.

The stabilizing and unstabilizing influences of neurogenic and vascular activities of the heart as related to sudden cardiac death.

Despite the frequency with which sudden cardiac death occurs in affluent societies, little is known about the precise mechanisms by which it is caused. Practically nothing is known about why sudden cardiac death occurs in one but not another person. It is difficult to escape the conclusion that in many instances, the final events occur almost by chance. Therefore, it would appear that every effort should be made by the physician to assist in preventing the changes, that is, cardiomegaly and myocardial ischemia, that appear to be potential markers of sudden cardiac death in many persons. Attention should be directed toward identifying and facilitating stabilizing neurogenic and vascular activities and identifying, controlling and reversing unstabilizing influences likely to foster sudden cardiac death. In the absence of a more complete knowledge of precise mechanisms, the efforts of the physician should be directed toward behavior modifications that appear to reduce the clinical manifestations of coronary heart disease which contribute to the development of cardiomegaly and myocardial ischemia.

Risk factors for cardiovascular disease and death: a clinical perspective.

Coronary artery disease has been demonstrated to conform to the principles of an epidemic disease. Therefore, the incidence of the occurrence of the disease is dependent in large part on "disturbances of human culture." These primarily include a cholesterol-rich diet, obesity, cigarette smoking, elevated blood pressure and sedentary life-style. It is gratifying that during the last quarter of a century, large segments of society in the United States have modified many of their adverse patterns of living. As a result, there has been a striking decline in both the incidence of the diagnosis of coronary artery disease and the frequency of premature death due to the disease process. Sudden cardiac death is frequently an unexpected first clinical manifestation of coronary artery disease and, despite heroic efforts, treatment of sudden death victims is frequently unsuccessful. Furthermore, progression of coronary artery disease, even in patients who present with angina pectoris or acute myocardial infarction, is unpredictable. Coronary arteriography, the "gold standard" used for evaluation, gives insight primarily into anatomy and ventricular function (under experimental conditions) existing at a given instant in time. Which lesions are serious and likely to progress are usually unknown, even to the most experienced angiographer. Therefore, surgical and catheter-directed therapeutic approaches are at best only "shotgun" or partial techniques. For these reasons, the principal and continuing therapeutic efforts to reduce the occurrence and control the ravages of coronary artery disease should be directed toward prevention. Such efforts should begin in early childhood and become a lifelong practice, one that all physicians, including the most procedure-dominated specialists, should personally adopt and teach.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethics in cardiovascular medicine. Task Force II: The relation of cardiovascular specialists to patients, other physicians and physician-owned organizations.

1. The American College of Cardiology acknowledges the continuum of changing societal, medical and economic perspectives affecting traditional medical ethics. Primacy of patient responsibility remains paramount to the cardiovascular specialist who at the same time should participate in the development of broader societal programs. 2. Medical decisions should be freely and jointly formulated by the patient and the cardiovascular specialist with appropriate sensitivity to such matters as mental competence, pertinent medical information and standards of care, sufficient time for contemplation, informed consent, patient right of refusal, physician right to refuse to provide inappropriate care and the right of patient, physician or third party payer to seek consultation or additional opinions. 3. The cardiovascular specialist should make a special effort to clarify and document patient preferences regarding end-of-life treatment through some form of advance directive. 4. The cardiovascular specialist bears a moral obligation to provide medical care to any patient who is HIV positive or has AIDS. 5. A conflict of interest occurs when a cardiovascular specialist places personal or financial interest ahead of the welfare and health of a patient. Professional accountability should be established through local or regional peer review. 6. The American College of Cardiology encourages and supports a renewed dedication to the principles of medical ethics, particularly in the field of cardiovascular disease. Cardiovascular specialists are encouraged to participate in the promulgation of medical ethics by teaching and by example, individually and with others.

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: 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.

Influence of aging on catecholamine levels, accumulation, and release in F-344 rats.

Neuronal function in selected brain areas has been evaluated in Fischer 344 rats aged 2-4 months, 11-14 months and 21-26 months. In vitro release of 3H-norepinephrine from hypothalamus and occipital cortex and 3H-dopamine from striatum has been evaluated using potassium, amphetamine, and field-stimulation. In vitro uptake of 3H-catecholamines has been evaluated in the same tissues. Catecholamine levels were measured in six brain areas: hypothalamus, striatum, cortex, cerebellum, brainstem and midbrain. Significant age-related decreases of NE levels, uptake, and release to high frequency stimulation were seen in the hypothalamus. The decreases in 3H-NE uptake and NE levels in the hypothalamus were apparent at 12 months, whereas the decrease in 3H-NE release after high frequency stimulation was seen in the senile rats.

Immunocytochemical localization of cannabinoid CB1 receptor and fatty acid amide hydrolase in rat retina.

Cannabinoids have major effects on central nervous system function. Recent studies indicate that cannabinoid effects on the visual system have a retinal component. Immunocytochemical methods were used to localize cannabinoid CB1 receptor immunoreactivity (CB1R-IR) and an endocannabinoid (anandamide and 2-arachidonylglycerol) degradative enzyme, fatty acid amide hydrolase (FAAH)-IR, in the rat retina. Double labeling with neuron-specific markers permitted identification of cells that were labeled with CB1R-IR and FAAH-IR. CB1R-IR was observed in all cells that were protein kinase C-immunoreactive (rod bipolar cells and a subtype of GABA-amacrine cell) as well as horizontal cells (identified by calbindin-IR). There was also punctate CB1R-IR in the distal one-third of the inner plexiform layer (IPL) that could not be assigned to a cell type. FAAH-IR was most prominent in large ganglion cells, whose dendrites projected to a narrow band in the proximal IPL. Weaker FAAH-IR was observed in the soma of horizontal cells (identified by calbindin-IR); the soma of large, but not small, dopamine amacrine cells (identified by tyrosine hydroxylase-IR); and dendrites of orthotopic- and displaced-starburst amacrine cells (identified by choline acetyltransferase-IR) but in less than 50% of the starburst amacrine cell somata. The extensive distribution of CB1R-IR on horizontal cells and rod bipolar cells indicates a role of endocannabinoids in scotopic vision, whereas the more widespread distribution of FAAH-IR indicates a complex control of endocannabinoid release and degradation in the retina.

Aortocoronary bypass grafting in the management of patients with coronary artery disease.

There is widespread agreement that aortocoronary bypass grafting generally lessens the symptoms and functional limitations of patients with angina pectoris. Evidence for prolongation of life or prevention of myocardial infarction, arrhythmias and ventricular dysfunction is inconclusive. Harmful effects associated with surgical management of coronary artery disease can be documented in terms of operative mortality, perioperative myocardial infarction, graft occlusion and progression of occlusive disease in the native circulation. In this review of published experience, the accomplishments and the limitations of myocardial revascularization are considered in various clinical settings. Critical assessment of evolving information leads to the conclusion that widespread application of this procedure beyond the alleviation of symptoms refractory to medical therapy is not justified by present data.

Education of the patient with cardiac disease in the twenty-first century: an overview.

The current status of education, behavioral change, and use of technology identifies a need for professionals who can develop interactive educational programs and apply existing techniques in a cost-effective manner. The general public, including patients with cardiac disease, are sophisticated consumers of information technology and demand quality production. The challenge is to train specialists to produce educational programs, to instruct health professionals in use of these programs, to deliver appropriate messages, to teach needed skills to patients with cardiac disease, and to evaluate the outcomes. Unless incentives to restore cardiac patients to an optimal functional status with few recurrences and complications are as tangible as are incentives for treating acute cardiac illnesses, the appropriate use of technology to educate patients with heart disease is unlikely to develop. However, the trend to increased ambulatory care under prospective payment systems makes it likely that technology will be applied to improve the efficiency in maintaining health and preventing acute illness. The potential benefits to the nation are substantial.

CB1 cannabinoid receptor: cellular regulation and distribution in N18TG2 neuroblastoma cells.

In order to characterize cellular regulation of CB1 cannabinoid receptors, synthesis and turnover studies were performed. Metabolic labeling of N18TG2 cells with 35S-labeled amino acids was followed by immunoprecipitation from cell lysates using an affinity-purified antibody generated to the N-terminal 14-amino-acid segment of the CB1 receptor. During a 2 h labeling period, CB1 receptors were rapidly and constitutively synthesized (rate: 0.86%/min). The majority of newly synthesized CB1 cannabinoid receptors (70%) was degraded rapidly by a first-order process (t1/2=4.8 h). The remaining nascent receptors, which were degraded slowly (t1/2>24 h), may represent the pool of potentially functional receptors. Trypsin treatment of intact confluent cells, designed to cleave the extracellular antibody recognition site, did not alter the recovery of metabolically labeled immunoprecipitated CB1 receptors. This suggests that a large percentage of newly synthesized receptors was inaccessible to the protease and is probably intracellular. Immunocytochemistry revealed CB1 cannabinoid immunoreactivity both intracellularly and on the cell surface. Subcellular membrane fractions exhibited receptor binding activity on plasma membranes and nuclear-associated membranes. Only low-affinity binding was seen in the chromatin fraction. An hypothesis has been developed to explain these results and form the basis for future studies.

GAP-43 in adult visual cortex.

GAP-43 was purified from cat brain by a rapid isolation procedure and was used to raise highly specific polyclonal antibodies in rabbits. Immunoblots of proteins from adult cat, monkey and human visual cortex as well as bovine cortex also showed specific staining of a single protein that was present in both soluble and membrane fractions. Immunocytochemistry of both cat and human adult visual cortex showed that GAP-43 has a laminar distribution.

GAP-43-like immunoreactivity in the adult retina of several species.

The localization of GAP-43-like immunoreactivity has been determined in retinas from adult toad, snake, rat, rabbit, cow and human. Specific labeling was conspicuous in discrete sublaminae within the inner plexiform layer of all mammalian species tested. In contrast, the toad retina exhibited punctate labeling in the outer plexiform layer, while the snake retina had little or no GAP-43-like immunoreactivity.

A clinical trial of a financial incentive to go to the tuberculosis clinic for isoniazid after release from jail.

SETTING: Screening for active tuberculosis (TB) and providing isoniazid (INH) preventive therapy in jails are important control measures. In San Francisco, however, historical data showed that 62% of inmates were released before completing preventive therapy, and of those only 3% attended the TB Clinic for follow-up. OBJECTIVE AND DESIGN: A randomized clinical trial to compare a $5 cash incentive plus standardized TB education with standardized TB education alone in encouraging released inmates to make a first visit to the clinic. RESULTS: Of 79 persons enrolled in the trial, 77.2% were released before INH completion. Rates of first visit were not significantly different for those receiving +5 plus standardized education (25.8%) versus standardized education alone (23.3%), but were higher than rates seen in historical data for inmates not receiving standardized education. Age was an important predictor of completion of a first visit (odds ratio 1.09, 95% confidence interval 1.02-1.16, P = 0.017). Other variables predicting adherence included intent to adhere, more previous time in jail, stable housing, and being partnered versus alone, although these were not statistically significant. CONCLUSION: Standardized education may be important in improving follow-up after release. Further work on the role of a financial incentive in this population is needed.

Triiodothyronine--binding immunoglobulin in a euthyroid patient.

We describe a clinically euthyroid 60-year old woman with a past history of 1311 therapy for treatment of possible toxic nodular goitre. She had an elevated thyroxine level of 188 microgram/L (normal range 50-125 microgram/L) following her therapy, and her TSH was within normal limits at 4.7 mU/L. However her T3 level, as determined by an RIA technique employing charcoal to separate bound and free T3, was not measurable. T3 added to the patient's serum could not be recovered, therefore the presence of an unusual protein capable of binding T3 was suspected. To avoid this interference, T3 analysis was performed on an ethanol extract of the patient's serum and was found to be 17 microgram/L (normal range 0.8-1.8 microgram/L). At this time her thyroid microsomal antibody titre was 1:100,000. A protein, capable of binding more than 70% of the patient's T3, was demonstrated in the gamma globulin fraction by agarose gel electrophoresis. This protein did not bind T4. Scatchard analysis for T3 binding revealed a protein, presumably IGG, with a binding affinity of 2 x 109 L/mole and binding capacity of 50 microgram/L. This case exemplifies the caution that must be taken in interpreting thyroid function tests. When thyroid hormone levels are inappropriate to the clinical status of the patient the presence of circulating antibodies which can bind the thyroid hormones should be considered.

An endogenous ligand to the benzodiazepine receptor: preliminary evaluation of its bioactivity.

Chromatographic separation of aqueous brain extracts yields a peptide containing fraction which competitively inhibits 3H-diazepam binding to its receptor. An intracerebral-ventricular injection of this isolated fraction results in altered responses in pharmacological and behavioral tests which are similar to those observed when diazepam is administered in the same fashion. The most pronounced effect was obtained in the conflict test. Changes observed in other tests, such as blocking pentylenetetrazole convulsions, altering motility or reducing hyperthermia, were also consistent with the actions of diazepam. At the dose used, neither diazepam nor the brain extract altered muscular co-ordination in two ataxia evaluations. Thus, the animals' performance in the other paradigms would not be adversely influenced by immobilization side-effects. The results reported here support the notion that an endogenous factor does exist in brain which can act like the benzodiazepine drugs when tested for bioactivity in animal studies.

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.