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PubMed2004

Knowledge of heart attack symptoms in 20 US communities. Results from the Rapid Early Action for Coronary Treatment Community Trial.

BACKGROUND: Effective treatment for patients with acute myocardial infarction is limited by patient delay in seeking care. Inadequate knowledge of heart attack symptoms may prolong delay. An intervention designed to reduce delay was tested in the Rapid Early Action for Coronary Treatment (REACT) Community Trial. In this report, the impact on knowledge of heart attack symptoms is presented. METHODS: Twenty communities were randomized to intervention or comparison status in a matched-pair design. Intervention strategies included community organization, public education, professional education, and patient education. The main outcome measures were based on information regarding knowledge of symptoms collected in a series of four random-digit-dialed telephone surveys. RESULTS: Knowledge of REACT-targeted symptoms increased in intervention communities. No change was observed in comparison communities. The net effect was an increase of 0.44 REACT-targeted symptoms per individual (P<0.001). The intervention effect was greater in ethnic minorities, persons with lower household incomes, and those with family or spouse history of heart attack (P<0.05). CONCLUSIONS: The REACT intervention was modestly successful in increasing the general public's knowledge of the complex constellation of heart attack symptoms. The intervention program was somewhat more effective in reaching disadvantaged subgroups, including ethnic minorities and persons with lower income. Despite these successes, the post-intervention level of knowledge was suboptimal.

Adolescent↗

PubMed2000

Psychological therapies for post-traumatic stress disorder.

BACKGROUND: After exposure to traumatic stressors, a subgroup of survivors (20-30%) will develop post-traumatic stress disorder (PTSD). AIMS: Since the incidence and prevalence rates for PTSD in the community are significant, it is important that general practitioners and psychiatrists be familiar with possible therapeutic options. In this review we shall look at the published evidence about the effectiveness of psychological treatments for PTSD. METHOD: The psychopathological mechanisms involved in PTSD are discussed. Studies of the effectiveness of different psychological therapies are reviewed. RESULTS: The review suggests that persistent fear or shame reactions are key aspects of PTSD. Evidence from systematic reviews suggests that psychotherapeutic treatments are effective in the therapy of reactions based on fear, and may increase the effectiveness of pharmacological therapy. There is less systematic evidence for the efficacy of interventions for symptoms based on shame. CONCLUSIONS: Although a proportion of patients with complex or chronic PTSD may require specialist interventions, most patients can be treated effectively by a general psychiatric service which can offer both pharmacological and psychological interventions.

Affective Symptoms↗

PubMed2001

Physical, functional and other non-pharmacological interventions for osteoarthritis.

Non-pharmacological interventions are frequently and widely used in the management of patients with osteoarthritis (OA). However, there is little evidence that most of these interventions are efficacious (i.e. that they work under ideal circumstances) owing to the paucity of research studies on these interventions and the fundamental methodological flaws in published studies. Moreover, the clinical effectiveness of non-pharmacological interventions (i.e. their efficacy under the conditions prevailing in clinical practice) is unknown, and cost-analysis of these interventions has not been carried out. If evidence-based management guidelines were to be constructed solely from firm research studies few could be recommended. Established and developing research methodologies and techniques should be employed to construct and conduct research programmes that appropriately evaluate the clinical and cost effectiveness of these complex non-pharmacological healthcare interventions. Establishing clinical effectiveness will ensure that we have practice-based evidence and are administering relevant, effective and optimal healthcare for patients with OA, maximizing the efficient use of healthcare resources.

Costs and Cost Analysis↗

PubMed1999

Coarctation of the Aorta.

Balloon angioplasty or early surgical correction is recommended once coarctation of the aorta has been diagnosed. Medical management is not a long-term option. The rate of restenosis is higher in infants and children than in adults, but the incidence of residual or late hypertension increases with age at initial intervention. Current angioplasty and stent placement techniques have reduced the rate of aneurysm formation and expanded the types of complex anatomic configurations amenable to nonsurgical intervention. Patients require long-term follow-up for restenosis and late or residual hypertension. Coarctation treatment is straightforward in patients with simple isolated coarctation. In neonates with associated lesions and diffuse arch hypoplasia, aggressive (albeit higher-risk) arch-enlargement procedures can be done at the time of open-heart correction of intracardiac defects. Changes in aortic compliance, vascular reactivity, and vascular homeostasis mechanisms in patients who have late surgery are associated with a higher incidence of residual hypertension.

Journal Article↗

PubMed2001

Postgenomic medicine. Presymptomatic testing for prediction and prevention.

Significant changes are occurring in genetic screening paradigms. Genetic screening is moving from traditional analytes, such as small molecules and proteins, to molecular genetic testing involving DNA and RNA. There are significant consequences to these changes, involving issues for the family unit, such as misattribution of parentage, and concerns regarding discrimination, confidentiality, and privacy. Although these latter issues have broader concerns for medicine and medical information, in the context of genetic testing, information derived from one individual can have a significant impact on others within their family. Screening is also changing from mendelian disease ascertainment to predictive testing. Issues that arise involve appropriate age at testing for adult-onset disorders, the clinical validity and clinical use of genetic testing for complex diseases, and the efficacy of interventions following genetic testing. We are also learning that the phenotypes of even simple mendelian disorders are influenced by complex genetic and environmental factors. The observations that genotypes rarely predict phenotypes absolutely have significant ramifications for counseling based on mutation analysis, for example in neonates who have not yet manifested symptoms and in older children and in adults undergoing predictive testing. Molecular genetic testing often proceeds rapidly from the research laboratory to the clinical setting. We must recognize that for single-gene disorders with high penetrance, the information derived from such testing may be relatively easy to interpret and apply. For complex diseases, however, the populations studied and their demographic characteristics are extremely important for extrapolation to counseling of individual patients. The value of population-based predictive testing is exemplified by newborn screening. It is clear that the Human Genome Project, and the information and technologies from it, will have a much broader impact on public health by presymptomatic prediction and prevention of disease.

Adolescent↗

PubMed2004

Donor-acceptor (electronic) coupling in the precursor complex to organic electron transfer: intermolecular and intramolecular self-exchange between phenothiazine redox centers.

Intermolecular electron transfer (ET) between the free phenothiazine donor (PH) and its cation radical (PH*+) proceeds via the [1:1] precursor complex (PH)(2)*+ which is transiently observed for the first time by its diagnostic (charge-resonance) absorption band in the near-IR region. Similar intervalence (optical) transitions are also observed in mixed-valence cation radicals with the generic representation: P(br)P*+, in which two phenothiazine redox centers are interlinked by p-phenylene, o-xylylene, and o-phenylene (br) bridges. Mulliken-Hush analysis of the intervalence (charge-resonance) bands afford reliable values of the electronic coupling element H(IV) based on the separation parameters for (P/P*+) centers estimated from some X-ray structures of the intermolecular (PH)(2)*+ and the intramolecular P(br)P*+ systems. The values of H(IV), together with the reorganization energies lambda derived from the intervalence transitions, yield activation barriers DeltaG(ET)() and first-order rate constants k(ET) for electron-transfer based on the Marcus-Hush (two-state) formalism. Such theoretically based values of the intrinsic barrier and ET rate constants agree with the experimental activation barrier (E(a)) and the self-exchange rate constant (k(SE)) independently determined by ESR line broadening measurements. This convergence validates the use of the two-state model to adequately evaluate the critical electronic coupling elements between (P/P*+) redox centers in both (a) intermolecular ET via the precursor complex and (b) intramolecular ET within bridged mixed-valence cation radicals. Important to intermolecular ET mechanism is the intervention of the strongly coupled precursor complex since it leads to electron-transfer rates of self-exchange that are 2 orders of magnitude faster (and activation barrier that is substantially lower) than otherwise predicted solely on the basis of Marcus reorganization energy.

Journal Article↗

PubMed1991

Intracranial aneurysms: interventional neurovascular treatment with detachable balloons--results in 215 cases.

Patients with complex or surgically difficult intracranial aneurysms are being treated with interventional neurovascular techniques. With neuroleptic anesthesia and a transfemoral femoral approach, a silicone micro-balloon can be flow directed through the intracranial circulation, guided directly into the aneurysm, and detached. The aneurysm is thus eliminated from the circulation, and the parent artery is preserved. For broad-based or ectatic aneurysms, test occlusion followed by permanent occlusion of the aneurysm and parent vessel can be performed. Since 1981, 211 patients with 215 aneurysms, including 177 cases involving the anterior and 38 cases involving the posterior circulation, have been treated with this technique. In 127 cases (59.1%), the parent vessel was occluded; in 88 cases (40.9%), primary occlusion of the aneurysm was achieved with preservation of the parent artery. Therapy-related complications included 21 deaths (9.8%) and 16 strokes (7.4%). Follow-up examinations were performed at 1, 3, and 12 months after treatment, and follow-up ranged from 5 months to 9 years. In patients in whom standard surgical therapy fails or for aneurysms in surgically inaccessible anatomic locations, interventional techniques that make use of detachable balloons may be a useful therapeutic alternative.

Adult↗

PubMed2006

Current management for epilepsy in tuberous sclerosis complex.

PURPOSE OF REVIEW: This article reviews the most significant advances in the field of epilepsy associated with tuberous sclerosis complex, with emphasis on new advances in the knowledge of the pathophysiological mechanisms of epileptogenicity, progress in identifying the epileptogenic zone, and the rationale for surgical management in individuals with intractable seizures. RECENT FINDINGS: Advances in our understanding of the mechanisms and genetics underlying infantile spasms and catastrophic epilepsy associated with tuberous sclerosis complex may facilitate more effective interventions. Early effective seizure control could significantly reduce the adverse developmental effects of chronic epilepsy in tuberous sclerosis. Vigabatrin is the first choice in the short-term treatment of infantile spasms. Some individuals, however, develop seizures that remain highly intractable. The factors that influence the intractability of epilepsy associated with tuberous sclerosis complex remain poorly understood. Multimodality neuroimaging has improved detection of epileptogenic foci, allowing an increased number of individuals to be evaluated for resective surgery. Epilepsy surgery is often associated with significant improvement of the neurologic outcome. SUMMARY: Epilepsy in tuberous sclerosis seems to arise from the interaction between multiple areas, all of which have increased excitability and reduced inhibition. Understanding the mechanisms of epileptogenesis might increase the availability of development of a more specific and efficacious treatment. New evidence suggests that it is possible to noninvasively identify children with tuberous sclerosis who are highly likely to become seizure free following surgical treatment.

Animals↗

PubMed1999

Congenital heart disease: six decades of progress.

Congenital heart malformations occur in approximately 1 in 100 live births. Since Robert Gross successfully ligated a persistent ductus arteriosus 60 years ago, there has been enormous progress in the surgical management of even the most complex lesions. More recently, the interventional cardiologist armed with balloons, stents, coils, umbrellas, and laser beams is providing an alternative to surgery for many lesions. Echocardiography combined with Doppler studies is now the most informative diagnostic modality, and its usefulness is being expanded by transesophageal studies. Magnetic resonance imaging is helpful for some lesions not well visualized on echo. Some complex lesions continue to challenge caregivers, especially the hypoplastic left heart syndrome and several variants of pulmonary atresia. Neurological complications in patients with congenital heart disease are not uncommon and are the main theme of this issue.

Cardiac Surgical Procedures↗

PubMed1997

Short-course, low-dose amphotericin B lipid complex therapy for visceral leishmaniasis unresponsive to antimony.

BACKGROUND: Visceral leishmaniasis (kala-azar) is a worldwide, disseminated intracellular protozoal infection for which prolonged, conventional therapy with pentavalent antimony has become increasingly less effective. OBJECTIVE: To determine the efficacy and minimal effective dose of short-course therapy with amphotericin B lipid complex in visceral leishmaniasis. DESIGN: A randomized, open-label study. SETTING: Inpatient kala-azar treatment unit in the state of Bihar in northeast India, where visceral leishmaniasis is endemic. PATIENTS: 60 patients with active infection who had not responded to or who had relapse after receiving conventional (> 30 days) treatment with pentavalent antimony. INTERVENTION: Intravenous amphotericin B lipid complex was given once daily for 5 consecutive days by 2-hour infusion. Patients were randomly assigned to receive 1, 2, or 3 mg/kg of body weight per day (total doses of 5, 10, or 15 mg/kg, respectively). MEASUREMENTS: Clinical and parasitologic responses (the latter were measured by parasite density score of the splenic aspirate) were determined 14 days after treatment. Definitive responses were assessed 6 months after treatment according to clinical outcomes and findings on examination of bone marrow aspirate. RESULTS: All 60 patients responded to 5 days of treatment. Fourteen days after therapy, all patients had parasite-free splenic aspirates and were considered to have an apparent clinical and parasitologic response. Six months after therapy, definitive responses were documented in 16 of 19 (84% [95% Cl, 60% to 97%]), 18 of 20 (90% [Cl, 68% to 99%]), and 21 of 21 (100% [Cl, 84% to 100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively. CONCLUSION: Short-course therapy with low-dose amphotericin B lipid complex is effective for visceral leishmaniasis and is an important therapeutic alternative in the management of this serious intracellular protozoal infection.

Adolescent↗

PubMed1994

Comparing healthcare outcomes.

Governments are increasingly concerned to compare the quality and effectiveness of healthcare interventions but find this a complex matter. Crude hospital statistics can be dangerously misleading and need adjusting for case mix, but identifying and weighting the patient characteristics which affect prognosis are problematical for conceptual, methodological, and practical reasons. These include the inherently uncertain nature of prognosis itself and the practical difficulties of collecting and quantifying data on the outcomes of interest for specific healthcare interventions and known risk factors such as severity.

Data Collection↗

PubMed2006

Inhibitors of HIV-1 Tat-mediated transactivation.

The transactivation responsive (TAR) RNA is the 5'-leader sequence of the HIV-1 mRNA genome and interacts with the Tat protein during transcription. Tat and the positive transcription elongation factor (P-TEFb) complex bind to TAR to promote efficient transcription of the full-length HIV genome. In the absence of the TAR.Tat.P-TEFb interaction, viral transcription is inefficient, which makes this RNA-protein complex an important target for therapeutic intervention of HIV replication. Inhibitors of HIV-1 transactivation mainly target: 1) TAR RNA, 2) Tat protein and 3) Tat.P-TEFb complex. 1) Compounds against TAR RNA are the most numerous: besides cationic peptides, which were initially developed, recent advances in TAR binding inhibitors include oligonucleotide based-agents and small molecules. Specific research efforts are currently underway to increase cellular uptake. 2) By targeting the Tat protein, both transactivation and other Tat-mediated intra/extracellular functions are affected. Various biopolymeric drugs are reported to effectively inhibit Tat activity. In addition, Tat-targeted antibodies have recently been developed. 3) Intracellular proteins have been discovered to disrupt Tat.P-TEFb interaction, raising the chance of inhibiting HIV-1 transcription via novel mechanisms.

Anti-HIV Agents↗

PubMed2005

Pediatric patient surface doses in neuroangiography.

BACKGROUND: Neuroangiographic techniques (diagnostic and interventional) can be lengthy and complex and can be associated with high radiation entrance skin doses from fluoroscopy and digital subtraction angiography (DSA). OBJECTIVE: To measure entrance surface doses received by pediatric patients undergoing neuroangiographic procedures and to (1) compare these doses with thresholds for deterministic effects, (2) compare these doses with those reported in adults, and (3) to understand the dose relationships among diagnostic and interventional procedures, DSA and fluoroscopy. MATERIALS AND METHODS: A neurobiplane unit with fluoroscopic and DSA capabilities was used for all neuroangiographic procedures. An automated patient dosimeter, installed on both planes of the unit, calculated maximum surface dose. The dosimeter also recorded the number of angiographic frames and the length of fluoroscopy time for each procedure. RESULTS: This retrospective study analyzed entrance surface doses to 100 pediatric patients, 76 of whom underwent neuroangiographic diagnostic procedures and 24 of whom underwent neuroangiographic interventional procedures. The DSA acquisitions ranged from 44 frames to 1,428 frames per procedure and fluoroscopy times ranged from 1.1 to 85.6 min per procedure. The mean surface dose from fluoroscopy was 68.1 mGy (max: 397.1 mGy) in the frontal (PA) plane; in the lateral (LAT) plane, the mean surface dose was 40.9 mGy (max: 418.5 mGy). The mean surface doses from DSA were 263.1 and 126.9 mGy in the frontal and lateral planes, with maximum doses of 924.4 and 410.1 mGy, respectively. Mean fluoroscopy dose rates were 5.4 mGy/min in the PA plane and 4.7 mGy/min in the LAT plane. The DSA largely contributed to the overall procedural surface dose, accounting for 82% of the combined surface dose in the each of the imaging planes. CONCLUSION: The surface dose for each procedure measured in this study was found to be below thresholds for deterministic effects. Interventional procedures consistently yield the highest doses.

Adolescent↗

PubMed2006

Error reduction in surgical pathology.

CONTEXT: Because of its complex nature, surgical pathology practice is inherently error prone. Currently, there is pressure to reduce errors in medicine, including pathology. OBJECTIVE: To review factors that contribute to errors and to discuss error-reduction strategies. DESIGN: Literature review. RESULTS: Multiple factors contribute to errors in medicine, including variable input, complexity, inconsistency, tight coupling, human intervention, time constraints, and a hierarchical culture. Strategies that may reduce errors include reducing reliance on memory, improving information access, error-proofing processes, decreasing reliance on vigilance, standardizing tasks and language, reducing the number of handoffs, simplifying processes, adjusting work schedules and environment, providing adequate training, and placing the correct people in the correct jobs. CONCLUSIONS: Surgical pathology is a complex system with ample opportunity for error. Significant error reduction is unlikely to occur without a sustained comprehensive program of quality control and quality assurance. Incremental adoption of information technology and automation along with improved training in patient safety and quality management can help reduce errors.

Diagnostic Errors↗

PubMed1997

Comparison of coronary luminal quantification obtained from intracoronary ultrasound and both geometric and videodensitometric quantitative angiography before and after balloon angioplasty and directional atherectomy.

BACKGROUND: Debate exists regarding the relationship between angiographic and intracoronary ultrasound (ICUS) measurements of minimal luminal cross-sectional area after coronary intervention. We investigated this and the factors that may influence it by using ICUS and quantitative angiography. METHODS AND RESULTS: Patients who underwent successful balloon angioplasty (n=100) or directional atherectomy (n=50) were examined by using ICUS and quantitative angiography (edge-detection [ED] and videodensitometry [VID]) before and after intervention. Luminal damage postintervention was qualitatively graded into three categories based on angiographic results (smooth lumen, haziness, or dissection). Correlation of minimal luminal cross-sectional area measurements by ICUS and ED was .59 before and .47 after balloon angioplasty. Correlation between ICUS and VID was .50 before and .63 after balloon angioplasty. Postintervention, the difference between ICUS and VID was less than the difference between ICUS and ED (P<.01). Additionally, the correlation was .74 between ICUS and ED measurements and .78 between ICUS and VID measurements in the smooth lumen group, .46 and .63, respectively, in the presence of haziness, and .26 and .46, respectively, in lesions with dissection. Similar results were obtained after directional atherectomy: the agreement between ICUS and quantitative angiography deteriorated according to the degree of vessel damage, but less so with VID than ED. CONCLUSIONS: Complex morphological changes induced by intervention may contribute to discordance between the two quantitative imaging techniques. In the absence of ICUS, VID may be a complementary technique to ED in lesions with complex morphology after balloon angioplasty and directional atherectomy.

Aged↗

PubMed1996

Factors predicting re-referral following crisis intervention for community-based persons with developmental disabilities and behavioral and psychiatric disorders.

Characteristics of 98 clients re-referred to receive services from a community-based crisis intervention program were compared to those of program clients who were served during the same 5.25-year period who were not referred. The majority of re-referrals occurred because of the same challenging behavior causing initial referral. Eight-eight percent of re-referral clients received the additional referral by 2 years after initial discharge. For persons under 30, nonfamily residence and initial diagnosis of self-injurious behavior were the strongest predictors. For those over 30, the most important factor was aggression. Recidivism following crisis intervention appears to be a complex function of client characteristics and community capabilities.

Adult↗

PubMed1991

Interventional cardiology techniques for coronary artery disease.

This review updates and extends observations made in this journal in March 1988. The focus then was on percutaneous transluminal coronary angioplasty and the clinical results of its practical application. A concern was expressed that science lagged in solving the major problems of rethrombosis and restenosis. The NHLBI Bypass Angioplasty Revascularization Investigation (BARI) study was still in the planning phase. In 1991, the scene has changed. Interventional cardiology now embraces a multitude of different catheter devices--angioplasty, atherectomy, laser, stents. Basic scientists are increasingly involved in addressing the restenosis issue. Our national heart meetings are increasingly oriented towards molecular biology approaches to solving the remaining problems. The BARI trial has nearly completed patient entry, and we eagerly await its results. The cardiologist and surgeon are faced with increasingly complex decisions with respect to interventional technologies, involving not only whether to use them, but which ones.

Angioplasty, Balloon, Coronary↗

PubMed1994

The crumpled coronary: an enigma of arteriographic pseudopathology and its potential for misinterpretation.

A series of angioplasty cases is presented in which dynamic alterations in coronary artery configuration developed. These changes were suggestive of extensive, complex dissections. Several common features emerged in these cases of which interventional cardiologists should be aware. These features included complex vessel morphology (tortuous segments, anomalous takeoffs, and complex stenoses) and the use of certain types of PTCA hardware (Amplatz guiding catheters and 0.018-inch wires). This phenomenon, termed pseudo narrowing, remains largely unrecognized. Identification of these characteristics and employment of proper management strategies will ensure a good outcome in these situations when they arise.

Aged↗