Sacral Giant Cell Tumor Presenting as Low Back Pain in the Chiropractic Office: A Case Report.

Sacral giant cell tumors are a rare cause of low back pain and may be challenging to identify via routine clinical examination and radiography. A 47-year-old woman presented to a chiropractor with a one-month history of worsening low back pain with radiation to the posterior thighs, worsened with ambulation, and used a cane to walk. She previously saw an orthopedic surgeon and was diagnosed with lumbar spondylosis, having tried anti-inflammatory medications, exercises, and acupuncture without success. The chiropractor ordered lumbar magnetic resonance imaging which revealed an aggressive sacral lesion and referred the patient to an oncologist. The oncologist performed positron emission tomography/computed tomography and biopsy, confirming a sacral giant cell tumor. A surgical team recommended tumor resection, lumbosacral fusion, radiotherapy, and zoledronic acid infusion. Sacral giant cell tumors are rare and may be challenging to identify via routine radiography. These tumors are an important differential to consider for patients with unexplained lumbosacral symptoms unresponsive to care.

Lumbar Schwannoma as a Rare Cause of Radiculopathy in the Chiropractic Office: A Case Report.

Cauda equina tumors are rare, slow-growing, and typically benign. These tumors present with low back pain resembling disc displacement with radiculopathy and thus may go undiagnosed for months. A 52-year-old, otherwise healthy man presented to a chiropractor with a one-year history of worsening low back pain radiating to the right lower extremity, rated an 8/10 in severity and aggravated by recumbency. Previously, his primary care physician had ordered radiographs revealing mild lumbar degenerative changes, prescribed a non-steroidal anti-inflammatory medication, and referred him to an orthopedist and physical therapist. There had been no change in symptoms. Upon examination by the chiropractor, the patient had neurologic deficits, and due to progressive worsening, the chiropractor recommended magnetic resonance imaging (MRI), which the patient deferred due to cost. The chiropractor initiated a trial of care, with initial success; however, the patient's symptoms recurred, and he consented to an MRI. MRI revealed an intradural extramedullary lumbar tumor, and the chiropractor referred the patient to an oncologist, who referred the patient to a neurosurgeon. The neurosurgeon surgically removed the mass, with a biopsy confirming a schwannoma. The patient had significantly improved six weeks after surgery. This case highlights a patient with chronic low back pain for whom a chiropractor identified a cauda equina tumor and referred him for further evaluation and surgery. Clinicians should consider night pain and persistent symptoms, despite conservative care, as red flags warranting further investigation in those with low back pain. Providers should refer for neurosurgical evaluation when clinical and radiological findings suggest a cauda equina tumor.

Alternative to Body Surface Area as a Solution to Correct Systematic Bias in Pediatric Echocardiography z Scores.

BACKGROUND: Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. METHODS: In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. RESULTS: Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. CONCLUSIONS: BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

The burden of dental care in Amelogenesis Imperfecta paediatric patients in the UK NHS: a retrospective, multi-centred analysis.

PURPOSE: The burden of dental care in Amelogenesis Imperfecta (AI) has not been well described. This condition results in weak, discoloured and often sensitive teeth. Specialist paediatric care is available for AI patients in the UK, but treatment protocols and care provided are inconsistent. The aim of this study was therefore to analyse the provision of treatment and burden of care for children and families with AI across four Paediatric Dentistry centres in the UK. METHODS: A retrospective evaluation of AI patient clinical records across four UK consultant-led Paediatric Dentistry centres was completed. Frequency and duration of care were recorded along with treatment and experience of inhalation sedation, local and general anaesthetic. RESULTS: In total, 138 records were available for analysis. The average patient age at first referral was 7.7 years (range 1-16 years) and families travelled an average 21.8 miles per appointment (range 0.2-286 miles). Patients attended on average 4.5 appointments per year for 5.8 years. In total, 65.2% had experience of local anaesthetic, 27.5% inhalation sedation and 31.9% general anaesthetic. Dental treatment including restorations and extractions were commonly required on multiple teeth per patient. CONCLUSION: AI carries a high burden of specialist dental care to patients and families. Specialist centres are required to provide longitudinal, comprehensive care.

In Vitro Synergistic Inhibition of HT-29 Proliferation and 2H-11 and HUVEC Tubulogenesis by Bacopaside I and II Is Associated with Ca2+ Flux and Loss of Plasma Membrane Integrity.

We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb Bacopa monnieri, induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation, and further demonstrated a synergistic effect of a combination of bac I and bac II on the inhibition of breast cancer cell line growth. Here, we assessed the effects of bac I and II on the colorectal cancer HT-29 cell line, and mouse (2H-11) and human umbilical vein endothelial cell (HUVEC) lines, measuring outcomes including cell viability, proliferation, migration, tube formation, apoptosis, cytosolic Ca2+ levels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below IC50 values, caused a synergistic reduction of the viability and proliferation of HT-29 and endothelial cells, and impaired the migration of HT-29 and tube formation of endothelial cells. A significant enhancement of apoptosis was induced only in HUVEC, although an increase in cytosolic Ca2+ was detected in all three cell lines. Plasma membrane integrity was compromised in 2H-11 and HUVEC, as determined by an increase in propidium iodide staining, which was preceded by Ca2+ flux. These in vitro findings support further research into the mechanisms of action of the combined compounds for potential clinical use.

Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening.

Dipeptidyl aminopeptidases (DPAPs) are cysteine proteases that cleave dipeptides from the N-terminus of protein substrates and have been shown to play important roles in many pathologies including parasitic diseases such as malaria, toxoplasmosis and Chagas's disease. Inhibitors of the mammalian homologue cathepsin C have been used in clinical trials as potential drugs to treat chronic inflammatory disorders, thus proving that these enzymes are druggable. In Plasmodium species, DPAPs play important functions at different stages of parasite development, thus making them potential antimalarial targets. Most DPAP inhibitors developed to date are peptide-based or peptidomimetic competitive inhibitors. Here, we used a high throughput screening approach to identify novel inhibitor scaffolds that block the activity of Plasmodium falciparum DPAP1. Most of the hits identified in this screen also inhibit Plasmodium falciparum DPAP3, cathepsin C, and to a lesser extent other malarial clan CA proteases, indicating that these might be general DPAP inhibitors. Interestingly, our mechanism of inhibition studies indicate that most hits are allosteric inhibitors, which opens a completely new strategy to inhibit these enzymes, study their biological function, and potentially develop new inhibitors as starting points for drug development.

A prospective clinical study of regenerative endodontic treatment of traumatized immature teeth with necrotic pulps using bi-antibiotic paste.

AIM: To evaluate the treatment outcomes of a revitalization endodontic technique (RET) for the management of traumatized immature teeth with necrotic pulps in children. METHODOLOGY: Fifteen healthy children (age range = 7-10 years) with traumatized immature maxillary incisors with necrotic pulps treated with bi-antibiotic revitalization endodontic technique were prospectively assessed over approximately two years (mean = 22 months). One operator undertook all treatments, clinical reviews and standardized radiographic exposures with radiographic analysis being carried out by two calibrated experienced clinicians. Crown colour change was assessed using an objective published methodology. Wilcoxon signed-rank test was used to compare root lengths, root dentinal widths and apical foramen widths over time. RESULTS: Interoperator measurement reliability was consistently strong for all measurements. There was no significant difference in root lengths or root dentinal wall widths following RET. A significant difference in apical foramen widths was observed after 2 years (P = 0.013) with resolution of clinical signs of infection in all cases. Despite omitting minocycline and using Portland cement (nonbismuth containing cement), a noticeable crown colour change (yellower, redder and lighter), as measured by an objective colour measurement system with ΔE = 7.39, was recorded. Most patients, however, were satisfied with the aesthetic outcome. CONCLUSION: Traumatized immature teeth with necrotic pulps treated with revitalization endodontic technique did not demonstrate continuation of root development or dentine formation when assessed by periapical radiographs. However, apical closure and periodontal healing were observed. A measurable change in crown colour (yellower, redder and lighter), with mostly no aesthetic concern to the patients/parents, was also observed.

The effect of viewing video clips of paediatric local anaesthetic administration on the confidence of undergraduate dental students.

INTRODUCTION: Dental treatment for children requires not only technical skills, but also the knowledge and confidence to provide behaviour management to support children of differing ages and stages of development. It is not surprising then that dental students find treating children especially stressful. Paediatric dentistry training is therefore a vital element of the undergraduate dental curriculum. MATERIALS AND METHODS: Eighty-six fourth-year undergraduate dental students received standard lectures and seminars about behaviour management techniques for children having local anaesthetic. The students were then randomly divided into groups using cluster randomisation. The intervention group received an intervention-based around video clips (VCs) demonstrating behaviour management techniques (BMTs) for children receiving local anaesthetic The intervention and control groups completed self-administered questionnaires to determine their level of confidence in managing local anaesthetic for children. RESULTS: There was a statistically significant difference in the level of confidence between the groups immediately after the teaching intervention (P=.003) and at 4 months (P=.001) in favour of the video group. DISCUSSION: Previous studies on the use of video as a teaching aid have reported favourable results in terms of both student attitudes and learning outcomes. The results from this study confirm the benefits of this style of teaching paediatric behaviour skills in the undergraduate dental curriculum, and the benefits were maintained at 4 months. CONCLUSION: This study has demonstrated that VCs as an additional teaching aid are an effective method in improving students' confidence for BMTs when delivering local anaesthetic.

A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver.

SUMO-modification of nuclear proteins has profound effects on gene expression. However, non-toxic chemical tools that modulate sumoylation in cells are lacking. Here, to identify small molecule sumoylation inhibitors we developed a cell-based screen that focused on the well-sumoylated substrate, human Liver Receptor Homolog-1 (hLRH-1, NR5A2). Our primary gene-expression screen assayed two SUMO-sensitive transcripts, APOC3 and MUC1, that are upregulated by SUMO-less hLRH-1 or by siUBC9 knockdown, respectively. A polyphenol, tannic acid (TA) emerged as a potent sumoylation inhibitor in vitro (IC50 = 12.8 µM) and in cells. TA also increased hLRH-1 occupancy on SUMO-sensitive transcripts. Most significantly, when tested in humanized mouse primary hepatocytes, TA inhibits hLRH-1 sumoylation and induces SUMO-sensitive genes, thereby recapitulating the effects of expressing SUMO-less hLRH-1 in mouse liver. Our findings underscore the benefits of phenotypic screening for targeting post-translational modifications, and illustrate the potential utility of TA for probing the cellular consequences of sumoylation.

UCSF Small Molecule Discovery Center: innovation, collaboration and chemical biology in the Bay Area.

The Small Molecule Discovery Center (SMDC) at the University of California, San Francisco, works collaboratively with the scientific community to solve challenging problems in chemical biology and drug discovery. The SMDC includes a high throughput screening facility, medicinal chemistry, and research labs focused on fundamental problems in biochemistry and targeted drug delivery. Here, we outline our HTS program and provide examples of chemical tools developed through SMDC collaborations. We have an active research program in developing quantitative cell-based screens for primary cells and whole organisms; here, we describe whole-organism screens to find drugs against parasites that cause neglected tropical diseases. We are also very interested in target-based approaches for so-called "undruggable", protein classes and fragment-based lead discovery. This expertise has led to several pharmaceutical collaborations; additionally, the SMDC works with start-up companies to enable their early-stage research. The SMDC, located in the biotech-focused Mission Bay neighborhood in San Francisco, is a hub for innovative small-molecule discovery research at UCSF.

Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51.

BACKGROUND: Chagas Disease, a WHO- and NIH-designated neglected tropical disease, is endemic in Latin America and an emerging infection in North America and Europe as a result of population moves. Although a major cause of morbidity and mortality due to heart failure, as well as inflicting a heavy economic burden in affected regions, Chagas Disease elicits scant notice from the pharmaceutical industry because of adverse economic incentives. The discovery and development of new routes to chemotherapy for Chagas Disease is a clear priority. METHODOLOGY/PRINCIPAL FINDINGS: The similarity between the membrane sterol requirements of pathogenic fungi and those of the parasitic protozoon Trypanosoma cruzi, the causative agent of Chagas human cardiopathy, has led to repurposing anti-fungal azole inhibitors of sterol 14α-demethylase (CYP51) for the treatment of Chagas Disease. To diversify the therapeutic pipeline of anti-Chagasic drug candidates we exploited an approach that included directly probing the T. cruzi CYP51 active site with a library of synthetic small molecules. Target-based high-throughput screening reduced the library of ∼104,000 small molecules to 185 hits with estimated nanomolar K(D) values, while cross-validation against T. cruzi-infected skeletal myoblast cells yielded 57 active hits with EC(50) <10 µM. Two pools of hits partially overlapped. The top hit inhibited T. cruzi with EC(50) of 17 nM and was trypanocidal at 40 nM. CONCLUSIONS/SIGNIFICANCE: The hits are structurally diverse, demonstrating that CYP51 is a rather permissive enzyme target for small molecules. Cheminformatic analysis of the hits suggests that CYP51 pharmacology is similar to that of other cytochromes P450 therapeutic targets, including thromboxane synthase (CYP5), fatty acid ω-hydroxylases (CYP4), 17α-hydroxylase/17,20-lyase (CYP17) and aromatase (CYP19). Surprisingly, strong similarity is suggested to glutaminyl-peptide cyclotransferase, which is unrelated to CYP51 by sequence or structure. Lead compounds developed by pharmaceutical companies against these targets could also be explored for efficacy against T. cruzi.

The use of psychotherapeutic interventions by primary care GPs in Ireland in the treatment of their methadone patients: a grounded theory study.

BACKGROUND: The methadone protocol placed responsibility on general practitioners (GPs) for the methadone treatment of stabilised drug-addicted patients. The protocol emphasised a medico-pharmacological model with minor reference to psychotherapeutic treatment. AIM: This qualitative study investigated how primary care GPs in Ireland use psychotherapeutic interventions in the treatment of methadone patients. METHOD: A grounded theory methodology was used. FINDINGS: There is a wide variation in the beliefs and knowledge of methadone-prescribing GPs regarding the efficacy of psychotherapeutic interventions for patients on methadone maintenance. GPs do not formally integrate psychotherapeutic interventions into methadone patient treatment. Accessing psychotherapeutic services raises concerns for GPs in terms of availability, location and quality. Primary care GPs who offer methadone maintenance view opiate abuse as a health issue similar to other such issues within their community. They take a holistic view of their methadone patient and, without formal guidelines, develop individual approaches to the use of psychotherapeutic interventions. The absence of a framework for the use of psychotherapeutic interventions in primary care methadone treatment in Ireland militates against the development of a basis for improving practice.

Activation of inflammasomes by tumor cell death mediated by gold nanoshells.

Gold nanoshell-enabled photothermal therapy (NEPTT) utilizes the efficient thermal conversion of near infrared (NIR) light for the ablation of cancer cells. Cancer therapies that combine cell killing with the induction of a strong immune response against the dying tumor cells have been shown to increase therapeutic efficacy in the clearance and regression of cancers. In this study, we assessed the ability of dying cells generated by in vitro NEPTT to activate inflammasome complexes. We quantified levels of major danger-associated molecular patterns (DAMPs), including adenosine triphosphate (ATP), adenosine diphosphate (ADP), and uric acid, released from tumor cells treated by NEPTT. The amount of DAMPs released was dependent on the dose of nanoshells internalized by cells. However, under all the employed conditions, the levels of generated DAMPs were insufficient to activate inflammasome complexes and to induce the production of pro-inflammatory cytokines (i.e. IL-1ß). The results from this study provide insights into the development of nanoplasmonics for combining both photothermal therapy and immunotherapy to eradicate cancers.

Mining a cathepsin inhibitor library for new antiparasitic drug leads.

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼ 2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts.

An image-based assay for high throughput screening of Giardia lamblia.

Giardia lamblia is a protozoan parasite that causes widespread gastrointestinal illness. Drugs to treat giardiasis are limited, but efforts to discover new anti-giardial compounds are constrained by the lack of a facile system for cell culture and inhibitor testing. We achieved robust and reproducible growth of G. lamblia in 384-well tissue culture plates in a modified TYI-S-33 medium. A high throughput assay for the screening of potential anti-giardial compounds was developed utilizing the WB strain of G. lamblia and automated optical detection of parasites after growth with tested inhibitors. We screened a library of 1600 known bioactive molecules and identified 12 compounds that inhibited growth of G. lamblia at low- or sub-micromolar concentrations. Our high throughput assay should facilitate evaluation of available chemical libraries for novel drugs to treat giardiasis.

S-nitrosylation of cyclin-dependent kinase 5 (cdk5) regulates its kinase activity and dendrite growth during neuronal development.

Precise regulation of cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is critical for proper neuronal development and functions. Cdk5 is activated through its association with the neuron-specific activator p35 or p39. Nonetheless, how its kinase activity is regulated in neurons is not well understood. In this study, we found that Cdk5 activity is regulated by S-nitrosylation, a post-translational modification of protein that affects a plethora of neuronal functions. S-nitrosylation of Cdk5 occurs at Cys83, which is one of the critical amino acids within the ATP-binding pocket of the kinase. Upon S-nitrosylation, Cdk5 exhibits reduced kinase activity, whereas mutation of Cys83 to Ala on Cdk5 renders the kinase refractory to such inhibition. Importantly, S-nitrosylated Cdk5 can be detected in the mouse brain, and blocking the S-nitrosylation of Cdk5 in cultured hippocampal neurons enhances dendritic growth and branching. Together, our findings reveal an important role of S-nitrosylation in regulating Cdk5 kinase activity and dendrite growth in neurons during development.

Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas' disease.

Chagas' disease, caused by infection with the parasite Trypanosoma cruzi, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells. T. cruzi-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4',6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of T. cruzi per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against T. cruzi. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.

Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal-medial thickness in patients with coronary heart disease.

BACKGROUND: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. AIM: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal-medial thickness (IMT) and inflammatory markers in patients with CHD. DESIGN: Randomised trial. SETTING: Single centre. PATIENTS: 112 patients with angiographic evidence of CHD. INTERVENTIONS: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. MAIN OUTCOME MEASURES: Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. RESULTS: The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). CONCLUSIONS: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.

Staphylococcus aureus capsular polysaccharide type 5 conjugate and whole cell vaccines stimulate antibody responses in cattle.

Dairy heifers were immunized subcutaneously with one of four different vaccines which contained preparations of Staphylococcus aureus capsular polysaccharide type 5 (CP5) and a mineral oil adjuvant, or received a placebo containing saline and adjuvant. The vaccine containing a CP5-human serum albumin conjugate (CP5-HSA) and the vaccine with formaldehyde inactivated whole cells expressing CP5, both elicited strong anti-CP5 antibody responses. After two injections three weeks apart and a third injection 10 months later, the mean level and duration of the anti-CP5 antibody response was significantly higher in the whole cell group. No differences were found between the two groups with regard to the relative proportion of IgG subclasses, and the antibody responses to the polysaccharide were composed of both the IgG1 and IgG2. Vaccines containing only free CP5 or CP5 mixed with HSA produced weak and transient humoral immune responses. Only animals vaccinated with the whole cell vaccine or the conjugate vaccine showed responses to CP5 in a lymphocyte proliferation assay conducted one year after the third vaccination. This study indicates that CP5 expressed on the surface of formaldehyde inactivated whole cells, emulsified in an oil adjuvant, gives a strong and long lasting immune response in cattle. The use of conjugation technology, although effective, might not be necessary in order to achieve an immune response against S. aureus CP5 in cattle.

Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial.

OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high-risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit.