Current Clinical Information Research Articles

Perioperative Anesthetic Care of the Obese Patient

Mayo Clinic, Rochester, Minnesota. mcglinch.brian@mayo.eduEdited by Vilma E. Ortiz, M.D., and Jeanine Wiener-Kronish, M.D. New York, Informa Healthcare USA, Inc., 2010. Pages: 234. Price: $300.00.Obesity affects all aspects of perioperative care in all age groups. Obese patients undergoing bariatric surgery typically have thorough preoperative evaluations and preconditioning preparations, making their anesthetic management routine. The clinical anesthesia challenge is that most morbidly obese patients having surgery do not undergo bariatric procedures. As a result, anesthesia providers are faced with both technical and clinical challenges in managing morbidly obese patients for procedures not involving weight loss, often without sufficient experience or insight into mitigating risk beyond those related to airway management.Perioperative Anesthetic Care of the Obese Patient provides an extraordinary amount of relevant information regarding obesity that is easily digested and applied in most perioperative settings. This informative and concise textbook is divided into sections (Preoperative, Intraoperative, Postoperative, and Special Situations), with each section addressing important clinical and physiologic aspects of care encountered in that venue. The editing is exceptional in that very little repetition or conflicting information is presented, and the information is well organized and thoughtfully presented.In the Preoperative section, each organ system is represented from the perspective of basic physiology and the organic dysfunction resulting from obesity. The information presented emphasizes observations reported from recent, obesity-related human studies relevant to a particular organ system. This section effectively balances basic science background and clinical studies, allowing the clinician an unbiased presentation of information relevant to obesity and anesthetic management. A busy clinician can reference a particular chapter and quickly access useful information, making this a valuable reference tool in clinical practice.The Intraoperative section is as useful and relevant as the preceding one. Obesity creates a challenging environment for anesthesia personnel, not only because of the need for appropriate drug dosing but also for issues related to positioning, monitoring, and regional anesthesia procedures. These topics are concisely and thoroughly presented. Much like the Preoperative chapters, the Intraoperative chapters emphasize clinical studies without becoming a “How To” atlas. I believe the great beauty of this book is that the reader is given the information necessary to understand the relevant challenges of intraoperative management of the obese patient without being distracted by authors advocating their point of view. The important issues are distilled, presented to the reader without bias, and can be readily referenced if intraoperative issues arise in clinical practice.The Postoperative section reaffirms the fact that obese patients present unique challenges (respiratory, infection, analgesia, and thromboembolic) after surgery but not necessarily greater morbidity or mortality. Postoperative management (e.g. , oxygen therapy, ambulation, deep venous thrombosis prophylaxis, and analgesia) of the obese patient is certainly more difficult than in the physically fit patient. However, in terms of morbidity and mortality of the obese patient after surgery, there are no overwhelming data suggesting the obese patient is at higher risk than the nonobese patient. This section carefully presents clinical data addressing common issues during both the early and late postoperative periods for the obese surgical patient. The section on critical care is an honest appraisal of clinical care for the critically ill obese patient and common obesity-related management challenges in the intensive care setting. With emphasis on clinical studies, the information is unbiased, honest, and clearly presented to the reader.The Special Situations section presents the implications for anesthetic management of the obese patient in the labor and delivery ward, pediatric anesthesia practice, and trauma care. As in the other sections, each topic is focused on relevant recent clinical studies without author bias endorsing one approach or technique over another. The authors avoid stating obvious and basic information, instead focusing on key concepts and observations made in cited references.I strongly recommend this book for not only anesthesia providers but also departmental libraries. The information is certainly not as extensive as that provided by the major anesthesiology textbooks, but the focused review of current clinical information regarding the effect of obesity on organ function and anesthetic management makes this book invaluable. Congratulations to the authors and editors for producing this much-needed, high-quality text.

Neue internationale Klassifikation der Hornhautdystrophien

The Cornea Society founded an international committee of 17 corneal experts from the USA, Asia and Europe in 2005. The goal of this group was to develop a new international classification of corneal dystrophies (CD) based on modern clinical, histological and genetic knowledge. Both authors are members of this committee. The elaboration of the classification included the correction of many misinterpretations with regard to the different forms of CD which were published in the past literature. In spite of important results concerning the genetic locus and identification of genes and mutations, corneal dystrophies are typically classified with respect to the level of the cornea that is involved. An accurate and up-to-date template for each form of the 25 CDs was created that included the current clinical, histological and genetic information. To indicate the level of evidence supporting the existence of a given dystrophy, the CDs are divided into four different categories. The new international classification of CDs was published in English, Spanish and German as a 40 page supplement with 64 figures, mostly in color. A more detailed description of genetic mutations is included in the appendix.

Predicting Phenotypic Severity of Uncertain Gene Variants in the RET Proto-Oncogene

Although reported gene variants in the RET oncogene have been directly associated with multiple endocrine neoplasia type 2 and hereditary medullary thyroid carcinoma, other mutations are classified as variants of uncertain significance (VUS) until the associated clinical phenotype is made clear. Currently, some 46 non-synonymous VUS entries exist in curated archives. In the absence of a gold standard method for predicting phenotype outcomes, this follow up study applies feature selected amino acid physical and chemical properties feeding a Bayes classifier to predict disease association of uncertain gene variants into categories of benign and pathogenic. Algorithm performance and VUS predictions were compared to established phylogenetic based mutation prediction algorithms. Curated outcomes and unpublished RET gene variants with known disease association were used to benchmark predictor performance. Reliable classification of RET uncertain gene variants will augment current clinical information of RET mutations and assist in improving prediction algorithms as knowledge increases.

Speaking the Same Language: Is It Possible to Educate Every Obstetric Nurse and Physician in Arkansas on the Current Fetal Heart Monitoring Terminology?

Tesa Ivey, MSN, APN TLIvey@uams.edu Background With numerous rural hospitals struggling to remain open, often the continuing education budget and the nurse educator position are the first things slashed. This creates a problem for rural nurses and physicians to remain current on changes in obstetrical practice. The University of Arkansas for Medical Sciences (UAMS) Rural Hospital Program and ANGELS (Antenatal & Neonatal Guidelines, Education & Learning System) are partners to provide a seamless network of current obstetrical and neonatal clinical information to rural providers throughout Arkansas.

A review of human factors principles for the design and implementation of medication safety alerts in clinical information systems.

The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many basic human factors principles are not followed, possibly contributing to the lack of acceptance of alerts in clinical information systems. We evaluate the limitations of current alerting philosophies and provide recommendations for improving acceptance of alerts by incorporating human factors principles in their design.

Long Head of the Biceps Tendon Pain: Differential Diagnosis and Treatment

Though the role of the long head of the biceps tendon (LHBT) in shoulder pathology has been extensively investigated, it remains controversial. Historically, there have been large shifts in opinions on LHBT function, ranging from being a vestigial structure to playing a critical role in shoulder stability. Today, despite incomplete understanding of its clinical or biomechanical involvement, most investigators would agree that LHBT pathology can be a significant cause of anterior shoulder pain. When the biceps tendon is determined to be a significant contributor to a patient's symptoms, the treatment options include various conservative interventions and possible surgical procedures, such as tenotomy, transfer, or tenodesis. The ultimate treatment decision is based upon a variety of factors, including the patient's overall medical condition, severity, and duration of symptoms, expectations, associated shoulder pathology, and surgeon preference. The purpose of this manuscript is to review current anatomic, functional, and clinical information regarding the LHBT, including conservative treatment, surgical treatment, and postsurgical rehabilitation regimens. Level 5.

The Gut Microbiota Predispose to the Pathophysiology of Acute Postradiotherapy Diarrhea

Severe diarrhea may complicate pelvic radiotherapy and force interruption of treatment. As there is no current clinical or experimental information on the role of the gut microbiota in this pathogenesis, we conducted a pilot observational study on the fecal microbiota in patients receiving pelvic radiotherapy. The study involved 10 patients who underwent 5 wk of radiotherapy for abdominal tumors and 5 controls. Four fecal samples were collected from each individual: before, during, at the end, and 2 wk after treatment. Following the amplification of the bacterial 16S rRNA gene from the samples, DNA fingerprinting and cloning-sequencing techniques were used to determine their microbial profile and composition, respectively. Six patients suffered acute postradiotherapy diarrhea and 4 did not. In patients without diarrhea, as well as in healthy volunteers, microbial diversity was stable over a period of 7 wk. However, patients exhibiting diarrhea showed a progressive modification in their microbial diversity. A radical drop in similarity index was observed at the end (P= 0.026) and still 2 wk after radiotherapy (P= 0.014). Interestingly, cluster analysis of the microbial profile in the first sample (S1) (collected before radiotherapy) displayed a dendogram where patients that presented diarrhea clustered separately from those that did not develop diarrhea after radiotherapy. Moreover, sequence analysis of dominant bacteria in the S1 sample confirmed differences between the diarrhea and nondiarrhea groups. In this set of patients, susceptibility or protection against diarrhea after radiotherapy could be linked to different initial microbial colonization.

Valproic acid poisoning: An evidence-based consensus guideline for out-of-hospital management

A review of US poison center data for 2004 showed over 9000 ingestions of valproic acid. A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected ingestion of valproic acid by 1) describing the process by which an ingestion of valproic acid might be managed, 2) identifying the key decision elements in managing cases of valproic acid ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to the acute ingestion and acute-on-chronic ingestion of immediate-release and extended-release dosage forms of valproic acid, divalproex, and valproate sodium alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This review focuses on the ingestion of more than a single therapeutic dose and the effects of an overdose. Although therapeutic doses of valproic acid can cause adverse effects in adults and children, some idiosyncratic and some dose-dependent, these cases are not considered. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in whom a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) Patients who are symptomatic (more than somnolence or exhibiting coma or seizures) after a valproic acid ingestion should be referred to an emergency department (Grade C). 3) Asymptomatic patients with an unintentional acute ingestion of 50 mg/kg or more or asymptomatic patients who are taking the drug therapeutically and who take an additional single acute ingestion of 50 mg/kg or more of any valproic acid formulation should be referred to an emergency department for evaluation (Grade C). 4) Patients with unintentional ingestions of immediate-release valproic acid formulations, who are asymptomatic, and more than 6 hours has elapsed since the time of ingestion, can be observed at home (Grade C). 5) Patients with unintentional ingestions of delayed-release or extended-release formulations of valproic acid who are asymptomatic, and more than 12 hours has elapsed since the time of ingestion, can be observed at home (Grade C). 6) Pregnant women who ingest below the dose for emergency department referral and do not have other referral conditions should be directed to their primary care obstetrical provider for evaluation of potential maternal and fetal risk. Routine referral to an emergency department for immediate care is not required (Grade D). 7) Do not induce emesis (Grade C). 8) Activated charcoal can be administered to asymptomatic patients who have ingested valproic acid within the preceding hour (Grade C). Prehospital activated charcoal administration, if available, should only be carried out by health professionals and only if no contraindications are present. Poison centers should follow local protocols and experience with its use. Do not delay transportation in order to administer activated charcoal (Grades D). 9) In patients who have ingested valproic acid and who are comatose, naloxone can be considered for prehospital administration in the doses used for treatment of opioid overdose, particularly if the patient has respiratory depression (Grade C). 10) A benzodiazepine can be administered by EMS personnel if convulsions are present and if authorized by EMS medical direction, expressed by written treatment protocol or policy, or if there is direct medical oversight (Grade C).

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

BackgroundThere are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message.Methods/designThe design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with informed, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension.For each of the three replicates there will be three intervention groups. The first group will receive informed with an attached postcard-sized, short, directive "outsert." The second intervention group will receive informed with a two-page explanatory "insert" on the same topic. The third intervention group will receive informed, with both the above-mentioned outsert and insert. The control group will receive informed only, without either an outsert or insert.Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours.A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling.Trial registration numberCurrent controlled trial ISRCTN72772651.

Modifying the Epigenome as a Therapeutic Strategy in Myelodysplasia

The term epigenetics refers to a number of biochemical modifications of chromatin that, without altering the primary sequence of DNA, have a role in genomic regulation and in particular gene expression control. These modifications can occur at the DNA level (i.e., DNA methylation), and affect the chromatin protein scaffold (i.e., histone code modifications), among several others. The study of these modifications is a very active area of research both at the basic and clinical levels. Clinical interest in these epigenetic alterations stems mainly from two observations. First, detection of specific epigenetic alterations could be used to develop cancer biomarkers (e.g., for the early detection or prognostication of cancer). Second, most epigenetic alterations are reversible both in vitro and in vivo, leading the way to the development of new anticancer therapies. This review focuses on the current clinical information regarding different forms of epigenetic therapy in patients with myelodysplastic syndromes (MDS). Basic aspects of DNA methylation or histone code alterations are not covered in detail in this review.

Methylphenidate poisoning: An evidence-based consensus guideline for out-of-hospital management

Methylphenidate poisoning: An evidence-based consensus guideline for out-of-hospital management

Clinical, Biochemical, and Genetic Heterogeneity in Short-Chain Acyl-Coenzyme A Dehydrogenase Deficiency

Short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) deficiency (SCADD) is an autosomal recessive, clinically heterogeneous disorder with only 22 case reports published so far. Screening for SCADD is included in expanded newborn screening programs in most US and Australian states. To describe the genetic, biochemical, and clinical characteristics of SCADD patients in the Netherlands and their SCADD relatives and to explore the genotype to phenotype relation. Retrospective study involving 31 Dutch SCADD patients diagnosed between January 1987 and January 2006 and 8 SCADD relatives. SCADD was defined by the presence of (1) increased butyrylcarnitine (C4-C) levels in plasma and/or increased ethylmalonic acid (EMA) levels in urine under nonstressed conditions on at least 2 occasions, in combination with (2) a mutation and/or the c.511C>T or c.625G>A susceptibility variants on each SCAD-encoding (ACADS) allele. Patients were included only if the SCAD-encoding (ACADS) was fully sequenced and if current clinical information could be obtained. Relatives were included when they carried the same ACADS genotype as the proband, and had increased C4-C and/or EMA. Prevalence, genotype (mutation/mutation, mutation/variant, variant/variant), C4-C and EMA levels, clinical signs and symptoms, and clinical course. A birth-prevalence of at least 1:50,000 was calculated. Most patients presented before the age of 3 years, with nonspecific, generally uncomplicated, and often transient symptoms. Developmental delay, epilepsy, behavioral disturbances, and hypoglycemia were the most frequently reported symptoms. The ACADS genotype showed a statistically significant association with EMA and C4-C levels, but not with clinical characteristics. Seven out of 8 SCADD relatives were free of symptoms. SCADD is far more common than assumed previously, and clinical symptoms in SCADD are nonspecific, generally uncomplicated, often transient, and not correlated with specific ACADS genotypes. Because SCADD does not meet major newborn screening criteria, including a lack of clinical significance in many patients and that it is not possible to differentiate diseased and nondiseased individuals, it is not suited for inclusion in newborn screening programs at the present time.

Implementation of hospital computerized physician order entry systems in a rural state: Feasibility and financial impact

The aim of this study was to estimate the costs of implementing computerized physician order entry (CPOE) systems in hospitals in a rural state and to evaluate the financial implications of statewide CPOE implementation. A simulation model was constructed using estimates of initial and ongoing CPOE costs mapped onto all general hospitals in Iowa by bed quantity and current clinical information system (CIS) status. CPOE cost estimates were obtained from a leading CPOE vendor. Current CIS status was determined through mail survey of Iowa hospitals. Patient care revenue and operating cost data published by the Iowa Hospital Association were used to simulate the financial impact of CPOE adoption on hospitals. CPOE implementation would dramatically increase operating costs for rural and critical access hospitals in the absence of substantial costs savings associated with improved efficiency or improved patient safety. For urban and rural referral hospitals, the cost impact is less dramatic but still substantial. However, relatively modest benefits in the form of patient care cost savings or revenue enhancement would be sufficient to offset CPOE costs for these larger hospitals. Implementation of CPOE in rural or critical access hospitals may depend on net increase in operating costs. Adoption of CPOE may be financially infeasible for these small hospitals in the absence of increases in hospital payments or ongoing subsidies from third parties.

Paediatric aphakic glaucoma

Aphakic glaucoma is a serious, sight-threatening complication in children who remain aphakic following congenital cataract surgery. The reported incidence varies from 15% to 45% and it has a higher incidence in small eyes and in babies who undergo surgery before 4 weeks of age. Most cases take the form of open-angle glaucoma. Despite careful monitoring, diagnostic difficulties in children may lead to delayed treatment. Aphakic children require ongoing monitoring, including examinations carried out under general anaesthesia. Contrary to earlier optimism, it is unlikely, according to current clinical information, that intraocular lenses provide protection against the development of glaucoma. It is likely that the lower incidence of glaucoma in pseudophakic eyes results from selection bias for lens insertion. Both medical and surgical treatments have a role in glaucoma management. Trabeculectomy with mitomycin C or Seton implantation (glaucoma drainage device) form the mainstay of surgical treatment. The success rate with Seton implants is better in the short term and more promising in the longer term than that of trabeculectomy. Cyclodestructive procedures play a role in refractory glaucoma. Success rates for surgery range from 14% to 44% and many children require additional medical treatment. Children with aphakic glaucoma need lifelong care. Despite our best efforts, many have poor vision, poor glaucoma control and ultimately become blind.

Hypoxia and Carcinoma of the Cervix.

The article examines current laboratory and clinical information with respect to the relative importance of tumor hypoxia to the radiation control of carcinoma of the cervix. Its impact is difficult to quantify because of interrelated important parameters, which are also operational, including inherent radiosensitivity, reoxygenation, repair, and clonogenic cell proliferation. Strategies that have been investigated to modify the detrimental affects of hypoxia are reviewed including laboratory and clinical data examining modifications of oxygen delivery by the use of blood transfusion, erythropoietin and perfluorochemicals. Clinical data supporting their beneficial effects are inconclusive although extrapolation from animal data suggests that raising hemoglobin levels in anaemic patients before radiotherapy may be useful. The possible benefits for the use of hyperbaric oxygen in conjunction with hypofractionated radiation are discussed. Preclinical and clinical data on the use of hypoxia cell radiation sensitizes are reviewed. No benefit has been shown for patients with carcinoma of the cervix when treated with hypoxic cell radiation sensitizers in conjunction with radiation. Possible future directions for investigation of strategies to overcome hypoxia are discussed.

Emergency department: Computerized provider order entry

In the fall of 2002, the emergency department (ED) leadership at Hartford Hospital requested a completely electronic patient record. The request included order entry, ED-specific documentation, patient tracking, and report generation. The current clinical information system offered provider order entry as a first step. The ED module of the current clinical system, including patient tracking and ED-specific documentation, was not yet available. The ED was to be the second computerized provider order entry (CPOE) unit in our hospital. The first was the pilot project on a 9-bed neurosurgical intensive care unit.

Calcium Channel Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management

In 2003, U.S. poison control centers were consulted after 9650 ingestions of calcium channel blockers (CCBs), including 57 deaths. This represents more than one-third of the deaths reported to the American Association of Poison Control Centers' Toxic Exposure Surveillance System database that were associated with cardiovascular drugs and emphasizes the importance of developing a guideline for the out-of-hospital management of calcium channel blocker poisoning. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of calcium channel blockers. An evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of calcium channel blockers alone and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. The panel's recommendations follow. The grade of recommendation is in parentheses. 1) All patients with stated or suspected self-harm or the recipient of a potentially malicious administration of a CCB should be referred to an emergency department immediately regardless of the amount ingested (Grade D). 2) Asymptomatic patients are unlikely to develop symptoms if the interval between the ingestion and the call is greater than 6 hours for immediate-release products, 18 hours for modified-release products other than verapamil, and 24 hours for modified-release verapamil. These patients do not need referral or prolonged observation (Grade D). 3) Patients without evidence of self-harm should have further evaluation, including determination of the precise dose ingested, history of other medical conditions, and the presence of co-ingestants. Ingestion of either an amount that exceeds the usual maximum single therapeutic dose or an amount equal to or greater than the lowest reported toxic dose, whichever is lower (see Table ), would warrant consideration of referral to an emergency department (Grade D). 4) Do not induce emesis (Grade D). 5) Consider the administration of activated charcoal orally if available and no contraindications are present. However, do not delay transportation in order to administer charcoal (Grade D). 6) For patients who merit evaluation in an emergency department, ambulance transportation is recommended because of the potential for life-threatening complications. Provide usual supportive care en route to the hospital, including intravenous fluids for hypotension. Consider use of intravenous calcium, glucagon, and epinephrine for severe hypotension during transport, if available (Grade D). 7) Depending on the specific circumstances, follow-up calls should be made to determine outcome at appropriate intervals based on the clinical judgment of the poison center staff (Grade D).

β-Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management

In 2003, US poison centers were contacted regarding ingestion of β-blockers by 15,350 patients including 3766 (25%) under 6 years of age; 7415 (48%) were evaluated in healthcare facilities and 33 died.An evidence-based expert consensus process was used to create this guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the primary author. The entire panel discussed and refined the guideline before its distribution to secondary reviewers for comment. The panel then made changes in response to comments received.The objective of this guideline is to assist US poison center personnel in the appropriate out-of-hospital triage and management of patients with suspected ingestions of β-blockers by describing the process by which a β-blocker ingestion might be managed, identifying the key decision elements in managing cases of β-blocker ingestion, providing clear and practical recommendations that reflect the current state of knowledge, and identifying needs for research.This guideline applies to ingestion of β-blockers alone and is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care, considering all of the circumstances involved.Recommendations are in chronological order of likely clinical use; the grade of recommendation is in parentheses. 1) Patients with stated or suspected self-harm or who are the victims of a potentially malicious administration of β-blocker should be referred to an emergency department immediately. In general, this should occur regardless of the dose reported (Grade D). 2) Patients without evidence of self-harm should have further evaluation, including determination of the precise dose ingested, history of other medical conditions, and the presence of co-ingestants. Ingestion of either an amount that exceeds the usual maximum single therapeutic dose or an amount equal to or greater than the lowest reported toxic dose (whichever is lower) warrants consideration of referral to an emergency department. Ingestion of any excess dose of any β-blocker in combination with a calcium channel blocker or the ingestion of any excess dose by an individual with serious underlying cardiovascular disease also warrants referral to an emergency department (Grade C). 3) Do not induce emesis. Consider the oral administration of activated charcoal if it is available and no contraindications are present but do not delay transportation to administer charcoal (Grade A). 4) Asymptomatic patients who ingest more than the referral dose should be sent to an emergency department if the ingestion occurred within 6 hours of contacting the poison center for an immediate-release product other than sotalol, within 8 hours of contacting the poison center for a sustained-release product, and 12 hours if they took sotalol (Grade C). 5) Ambulance transportation is recommended for patients who are referred to emergency departments because of the potential for life-threatening complications of β-blocker overdose. Provide usual supportive care en route to the hospital, including intravenous fluids for hypotension (Grade D). 6) Follow-up calls should be made to determine outcome at appropriate intervals for up to 12–24 hours based on the judgment of the poison center staff (Grade D). 7) Asymptomatic patients who are referred to healthcare facilities should be monitored for at least 6 hours after ingestion if they took an immediate-release preparation other than sotalol, 8 hours if they took a sustained-release preparation, and 12 hours if they took sotalol. Routine 24-hour admission of an asymptomatic patient who has unintentionally ingested a sustained-release preparation is not warranted (Grade D).

Bcl-2 antisense therapy in hematologic malignancies

Overexpression of the Bcl-2 oncoprotein is noted in various malignant disorders. In patients with hematologic malignancies, increased production of the Bcl-2 oncoprotein is associated with chemotherapy resistance, aggressive clinical course, and poor survival. Bcl-2 is an important molecular target. Downregulating Bcl-2 can potentially reverse inherent tumor resistance to, and possibly improve response to therapy. This review focuses on the preclinical data, as well as the current clinical information available on oblimersen, a novel antisense approach targeting Bcl-2 in malignant hematologic disorders. Early clinical trials have shown single-agent activity of oblimersen in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma, and thus, provide proof of principle for antisense therapy. Phase I and phase II studies using oblimersen in combination with conventional chemotherapy have shown encouraging results in patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute myeloid leukemia. Phase III studies in patients with multiple myeloma and chronic lymphocytic leukemia have completed accrual and results are awaited. Bcl-2 is a clinically meaningful target in patients with hematologic malignancies. Downregulation of the Bcl-2 oncoprotein can be achieved with oblimersen (antisense molecule specific for Bcl-2). Early clinical results suggest a possible role of this antisense approach in targeting Bcl-2. Ongoing clinical trials will establish the clinical utility of oblimersen in patients with hematologic malignancies.

PDxMD

PDxMD is a new and promising evidence-based electronic primary care clinical information resource. It is geared primarily to the physician, as is its companion database, MDConsult, but it can also be very useful to medical and non-medical librarians seeking to quickly summarize current, accurate, and quality-filtered clinical information focusing on diagnosis, therapy, prognosis, and prevention.