Clinical Management Issues Research Articles

Myasthenia in pregnancy: best practice guidelines from a UK multispecialty working group

A national UK workshop to discuss practical clinical management issues related to pregnancy in women with myasthenia gravis was held in May 2011. The purpose was to develop recommendations to...

Stress Ulcer Prophylaxis in the ICU

Bleeding from stress-related mucosal disease (SRMD) in critically ill patients remains an important clinical management issue. Although only a small proportion (2% to 6%) of patients admitted to an ICU setting will bleed (1), a significant proportion exhibit the clinical risk factors, mainly mechanical ventilation for more than 48 hrs and the presence of a coagulpathy (2), that predict a higher risk of bleeding; furthermore, upper gastrointestinal mucosal lesions can be found in 75% to 100% of ICU patients (3). Although uncommon, stress-ulcer bleeding (SUB) is a severe complication as it is estimated that up to 50% patients will die, mostly from decompensation of an underlying condition or multiorgan failure (4). The use of SUB prophylaxis remains a matter of concern, its efficacy has been questioned with, in addition, some concerns about the risk of adverse events such as nosocomial pneumonia and clostridium difficile infection (5). Several medications have been assessed, including sucralfate, histamine-2 receptor antagonists (H2RAs), and protonpump inhibitors (PPIs). As H2RAs were shown to be superior to sucralfate (6), use of prophylactic pharmacotherapy comes down to opting for H2RAs or PPIs—a choice that has remained controversial as the underlying pathophysiology of SRMD differs from that of bleeding peptic ulcers, relating less on acid secretion and more on decreased mucosal blood flow, local ischemia, hypoperfusion, and reperfusion injury (3). In this issue of Critical Care Medicine, Dr. Alhazzani et al (7), report a systematic review and meta-analysis on the use of H2RAs or PPIs for stress ulcer prophylaxis in critically ill patients. The authors conclude that PPIs compared with H2RAs are more effective at reducing clinically important upper gastrointestinal bleeding (relative risk [RR] 0.36; 95% CI 0.19, 0.68) and overt upper gastrointestinal bleeding (RR 0.35; 95% CI 0.21, 0.59), without significantly increasing the risk of nosocomial pneumonia (RR 1.06; 95% CI 0.73, 1.52; p = 0.76). PPIs, however, appear to reduce neither ICU mortality nor length of stay, confirming and expanding findings of our meta-analysis published earlier this year (8). The major strength of this study

Capsule Commentary on Waldura et al., Teleconsultation Improves Primary Care Clinicians’ Confidence about Caring for HIV

The study by Waldura et al. used an electronic survey to examine primary care clinicians’ self-perceived confidence and self-reported clinical practice patterns after using the University of San Francisco-based National Human Immunodeficiency Virus (HIV) Telephone Consultative Service (HIV Warmline).1 The HIV Warmline provides clinicians with no-cost, real-time telephone consultations with experts in HIV medicine. Over the two-year study period, the authors found that among the primary care clinicians (physicians and mid-level practitioners), most reported the HIV Warmline to be quicker, more applicable to their clinical management issues, and more trustworthy as compared with other HIV information sources. The majority reported that using the teleconsultation service increased their confidence in managing HIV patients, changed their HIV management, and decreased the likelihood of referral to an HIV specialist. This study provides an initial assessment of the potential clinical impact of the HIV Warmline, an innovative adjunct to clinical care. However, the study is ultimately limited in its scope, as its outcomes are subjective provider-reported measures. Patient-level data was not collected, so we do not know the range of complexity of the cases discussed on the Warmline. Although clinicians who used the Warmline reported more confidence and that they were less likely to refer their patients, it is unknown whether these self-perceived changes actually translated to lower rates of referral to specialists and, more importantly, whether they positively affected patient quality of care and clinical outcomes. Waldura et al.’s study is timely, as teleconsultation is becoming increasingly utilized to address disparities in access to specialty care.2–4 With regards to HIV care, the emergence of teleconsultation is occurring in the context of expanded HIV testing, an HIV care provider shortage and a paradigm shift in HIV care—from specialty care-based to primary care-based.5 Other existing teleconsultation models have had success in providing clinical support to primary care clinicians in settings with limited access to specialists,2–4 and have positively impacted clinical outcomes.4 While the HIV Warmline offers a promising approach to strengthening clinical support for HIV primary care clinicians in resource-constrained settings, data on its actual impact on patient quality of care and clinical outcomes is needed.

Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation

The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

Biology or Behavior: Which Is the Strongest Contributor to Weight Gain?

Combating unhealthy weight gain is a major public health and clinical management issue. The extent of research into the etiology and pathophysiology of obesity has produced a wealth of evidence regarding the contributing factors. While aspects of the environment are ‘obesogenic’, weight gain is not inevitable for every individual. What then explains potentially unhealthy weight gain in individuals living within an environment where others remain lean? In this paper we explore the biological compensation that acts in response to a reduced energy intake by reducing energy needs, in order to defend against weight loss. We then examine the evidence that there is only a weak biological compensation to surplus energy supply, and that this allows behavior to drive weight gain. The extent to which biology impacts behavior is also considered.

Health Functional Units Sentinel Network.A. Learning Device and Decision Support System in Health Functional Units at Portuguese Primary Health Care Level

The recent portuguese Primary Care (PC) reform initiated in 2006, was presented as an extraordinary event and a marker of decisive times in portuguese society, by implementing a new model of primary health care services. This model is based on the principles of decentralization, self-organization, achievement of healthcare quality goals and responsabilization of self- motivated teams. There are various kinds of functional health units which creation is based on those principles - care providing units such as Family Healthcare Units (FHU) and support units. It is necessary to mobilize the scientific and technological potential of FHU to endow of intelligence this massive changing process, so that the PC network continues to be a ‘living laboratory’ and acts as a generator of knew knowledge. The WHO World Health Report 2008 has articulated the need to mobilize the production of knowledge on primary care. After been contextualized with environment variables, valid and strategic information should be used as support for knowledge generation, for decision making chain and action. The lack of information and knowledge about clinical, scientific, epidemiologic, organizacional and health management issues due to changes recently introduced with the PHC reform, leeds to a need for globalized strategies of information dissemination that could support research, enlarge epidemiological surveillance and improve health governance. It is also imperative a continued focus on innovation and the existence of a tableau de board as device of continuous monitoring and periodic update. This paper proposes a health functional units sentinel network in order to retrieve, transform and load useful healthcare data to the portuguese primary health care system. The idea of creating sentinel healthcare units pretends to act as a learning device and a decision support system in the field of health data collection, which should be capable to extract relevant data in the source-systems, transfer it to data wharehouses or datacentres, analyze it using data mining and statistical tools and report the results as useful information products back to the FHU and other stakeholders. These procedures aim to produce high quality information that would be necessary to scientific research, surveillance and management.

The Generation Gap

When JACR was first published 10 years ago, most of the current radiology residents were in college, unaware of the intricacies of medical practice and the need for a radiology journal addressing issues in clinical practice, practice management, education, and health services research. It probably seems like yesterday to some, but 10 years is half a generation. Not only has the technology and practice of the specialty evolved in that time, the generational constituency of radiology has changed. In addition to the traditionalists (the silent or greatest generation), the baby boomers, and generation X, we now have generation Y, also known as the millennial generation, as part of the workforce [1]. Generation Y includes people born between approximately 1981 and 2005 [1]. Most of our medical students and residents are part of generation Y, children of the baby boomers. Perhaps some understanding of the characteristics that define this newest generation can help us work together with less frustration. Generation Y members had overscheduled, highly structured childhoods and were raised by parents who praised them for everything [2]. David McCullough Jr gave a commencement speech to the 2012 high school class of Wellesley, Massachusetts, an affluent suburb of Boston. The speech went viral because it resonated with people that someone told generation Y, “You’re not special” [3]:

Li-Fraumeni syndrome: report of a clinical research workshop and creation of a research consortium

Li-Fraumeni syndrome (LFS) is a rare dominantly inherited cancer predisposition syndrome that was first described in 1969. In most families, it is caused by germline mutations in the TP53 gene and is characterized by early onset of multiple specific cancers and very high lifetime cumulative cancer risk. Despite significant progress in understanding the molecular biology of TP53, the optimal clinical management of this syndrome is poorly defined. We convened a workshop on November 2, 2010, at the National Institutes of Health in Bethesda, Maryland, bringing together clinicians and scientists, as well as individuals from families with LFS, to review the state of the science, address clinical management issues, stimulate collaborative research, and engage the LFS family community. This workshop also led to the creation of the Li-Fraumeni Exploration (LiFE) Research Consortium.

Transfer of patients with ruptured abdominal aortic aneurysm from general hospitals to specialist vascular centres: results of a Delphi consensus study

AimTo explore areas of consensus and disagreement concerning the interhospital transfer of patients with a clinical diagnosis of ruptured abdominal aortic aneurysm.MethodsA three-round Delphi questionnaire approach was used among vascular...

Clinical Significance of Lymph Node Micrometastasis in Gastric Cancer

Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer.

Reflective Account of a Significant Event in Practice: A Student ODP's Perspective

This is an account of a significant event that occurred in clinical practice. The incident highlights issues that can arise from a breakdown of verbal and non-verbal communication between members of staff. It also demonstrates how professional conduct and effective team working can overcome such breakdowns to elicit a positive outcome. Using Johns (2009) model of structured reflection (MSR), this article reflects on the student operating department practitioner's (ST/ODP) role as anaesthetic support, exploring the impact on the care received by the patient, whilst examining the ethico-legal (governing body and legislation) considerations involved. Furthermore, the ST/ODP proposes to identify environmental and intra-operative factors that are potentially damaging to the patient's well being, through understanding the principles of negligence, emphasising clinical governance, vicarious liability and risk management issues.

Clinical decision making in a high-risk primary care environment: a qualitative study in the UK

ObjectiveExamine clinical reasoning and decision making in an out of hours (OOH) primary care setting to gain insights into how general practitioners (GPs) make clinical decisions and manage risk in...

Life-threatening clostridial infections

Life-threatening soft tissue infections caused by Clostridium species have been described in the medical literature for hundreds of years largely because of their fulminant nature, distinctive clinical presentations and complex management issues. The Clostridium species perfringens, septicum and histolyticum are the principal causes of trauma-associated gas gangrene and their incidence increases dramatically in times of war, hurricanes, earthquakes and other mass casualty conditions. Recently, there has also been an increased incidence of spontaneous gas gangrene caused by Clostridium septicum in association with gastrointestinal abnormalities and neutropenia. Similarly, over the last 15 years there has been increased recognition of a toxic shock-like syndrome associated with Clostridium sordellii in individuals skin-popping black tar heroin, in women undergoing childbirth or other gynecologic procedures including medically-induced abortion. Like their cousins Clostridium tetanus and Clostridium botulinum, the pathogenesis of these clostridial infections is largely the consequence of potent exotoxin production. Strategies to inhibit toxin production, neutralize circulating toxins and prevent their interaction with cells of the innate immune response are sorely needed. Recent studies have elucidated novel targets that may hold promise for newer therapeutic modalities.

Changing clinical profile, management strategies and outcome of patients with biliary tract injuries at a tertiary care center in Sri Lanka

Biliary tract injuries are mostly iatrogenic. Related data are limited in developing countries. There are lessons to be learned by revisiting the clinical profiles, management issues and outcome of patients referred to a tertiary care center in Sri Lanka, compared with the previous data from the same center published in 2006. Such a review is particularly relevant at a time of changing global perceptions of iatrogenic biliary injuries. This study aimed to analyze and compare the changes in the injury pattern, management and outcome following biliary tract injury in a Sri Lankan study population treated at a tertiary care center. A retrospective analysis was made of 67 patients treated between May 2002 and February 2011. The profiles of the last 38 patients treated from October 2006 to February 2011 were compared with those of the first 29 patients treated from May 2002 to September 2006. Definitive management options included endoscopic biliary stenting, reconstructive hepaticojejunostomy with creation of gastric access loops, and biliary stricture dilation. Post-treatment jaundice, cholangitis and abdominal pain needing intervention were considered as treatment failures. In the 67 patients, 55 were women and 12 men. Their mean age was 40.6 (range 19-80) years. Five patients had traumatic injuries. Thirty-seven injuries (23 during the second study period) were due to laparoscopic cholecystectomy and 25 (10 during the second study period) to open cholecystectomy. The identification rate of intra-operative injury was 19% in the laparoscopic group and 8% in the open group. Bismuth type I, II, III and IV injuries were seen in 18, 18, 15 and 12 patients, respectively. Endoscopic stenting was the definitive treatment in 20 patients. In 35 patients who had hepaticojejunostomy, 33 underwent creation of the gastric access loop. Twenty-two reconstructions were performed during the second study period. A gastric access loop was used for endotherapy in three patients with anastomotic occlusion at the site of hepaticojejunostomy. The overall outcome was satisfactory in the majority of patients. There were four injury-related deaths. Biliary tract injuries associated with laparoscopic cholecystectomy have become the most frequent cause of biliary injury management at our center. Although endotherapy was useful in selected patients, in the majority, surgical reconstruction with hepaticojejunostomy was required as the definitive treatment. Creation of the gastric access loop was found to be a useful adjunct in the management of hepaticojejunostomy strictures.

Depressive symptoms in first episode schizophrenia spectrum disorder

BackgroundDepressive symptoms in ‘non-affective’ first episode schizophrenia spectrum disorders (FES) are common, but poorly understood, resulting in a range of conceptual and clinical management issues. This study had three aims: (i) to determine the prevalence of moderate to severe depressive symptoms (defined as a Clinical Global Impressions Scale-Bipolar Disorder (CGI-BP depression) score >3) in a large representative sample of FES patients; (ii) to compare the clinical and functional characteristics of FES patients with and without these depressive symptoms at service entry; and (iii) to compare the characteristics of FES patients with and without persistent depressive symptoms. MethodsMedical file audit methodology was employed to collect information on 405 patients with FES treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Results26.2% (n=106) of the patients had moderate to severe depression at service entry. At service entry and at discharge, those with depressive symptoms had greater insight into their illness but did not differ from those without depressive symptoms in terms of severity of overall psychopathology. Substance use was significantly less common in those with depressive symptoms at service entry and at discharge. Of those who were depressed at baseline, 14.2% (n=15) continued to have moderate to severe depressive symptoms at discharge. DiscussionDepressive symptoms are common in patients with FES. Understanding the nature and characteristics of depression in FES has important clinical implications for both early intervention and treatment.

Metastatic endometrial stromal sarcoma of the lung: importance of immunohistochemical staining, clinical history and imaging studies

Proper evaluation of lung nodules is a difficult issue for clinical management of patients. Discriminating metastatic endometrial stromal sarcoma (ESS) from other primary spindle cell neoplasms of the lung using histological analysis can be challenging. This is particularly true when an adequate clinical history is lacking, because ESS metastasis can be delayed by a couple of decades. To emphasize the importance of the correlation of pathological findings with clinical history and imaging studies, we investigated 11 cases of ESS (seven low grade and four high grade) metastatic to the lung. All cases presented with one to multiple unilateral or bilateral lung nodules that were detected by chest computed tomography. Primary ESS was diagnosed from hysterectomy specimens except for one by endometrial biopsy, 0.5 to 23 years prior to metastasis. Immunohistochemical studies showed that all ESS cases were moderately to strongly positive for Bcl-2 and CD10 with > 50% of tumor cells stained, except for one high grade ESS that was negative for CD10. Eight (72.7%) and seven (63.6) of the 11 cases showed positive estrogen and progesterone receptors, respectively, with a majority of positive cases showing diffuse and moderate to strong staining. Strong but patchy staining for CD34 was detected in one (9.1%) case with smooth muscle differentiation. CK7 and TTF-1 were negative in all cases. Two (18.2%) cases exhibited patchy and strong positivity for caldesmon. Two (18.2%) low grade ESS cases showed moderate to strong AE1/AE3 positivity in > 50% of tumor cells, one of which also showed moderate CK19 and Cam 5.2 staining in >30% of tumor cells. One should be cautious when assessing spindle cell neoplasms of the lung in women with a history of hysterectomy. Correlation of clinical history and imaging studies with histological and immunohistochemical findings is essential to diagnosis of metastatic ESS to the lung.

Enter the reverend: introduction to and application of Bayes' theorem in clinical ophthalmology

Ophthalmic practice utilizes numerous diagnostic tests, some of which are used to screen for disease. Interpretation of test results and many clinical management issues are actually problems in inverse probability that can be solved using Bayes' theorem. Use two-by-two tables to understand Bayes' theorem and apply it to clinical examples. Specific examples of the utility of Bayes' theorem in diagnosis and management. Two-by-two tables are used to introduce concepts and understand the theorem. The application in interpretation of diagnostic tests is explained. Clinical examples demonstrate its potential use in making management decisions. Positive predictive value and conditional probability. The theorem demonstrates the futility of testing when prior probability of disease is low. Application to untreated ocular hypertension demonstrates that the estimate of glaucomatous optic neuropathy is similar to that obtained from the Ocular Hypertension Treatment Study. Similar calculations are used to predict the risk of acute angle closure in a primary angle closure suspect, the risk of pupillary block in a diabetic undergoing cataract surgery, and the probability that an observed decrease in intraocular pressure is due to the medication that has been started. The examples demonstrate how data required for management can at times be easily obtained from available information. Knowledge of Bayes' theorem helps in interpreting test results and supports the clinical teaching that testing for conditions with a low prevalence has a poor predictive value. In some clinical situations Bayes' theorem can be used to calculate vital data required for patient management.

Combined aliskiren-amlodipine treatment for hypertension in African Americans: clinical science and management issues

While it may seem at first that antihypertensive drug combinations run counter to the desire to 'personalize' the management of hypertension, the best combinations have predictable efficacy in different individuals and subpopulations. Race is probably not a valid surrogate for clinically meaningful genetic variation or guide to therapy. Most guidelines suggest similar blood pressure goals for different races but drug treatment recommendations have diverged. In the United States, race is not considered to be a major factor in drug choice, but in England and other countries, initial therapy with renin-angiotensin system blocking drugs is not recommended in Blacks. In this review we: (1) examine new trends in race-based research; (2) emphasize the weaknesses of race-based treatment recommendations; and (3) explore the effects of a new combination, renin inhibition (aliskiren) and amlodipine, in African Americans.

Prescription opioid abuse, pain and addiction: Clinical issues and implications

Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy.

Disseminated Mycobacterium kansasii infection with hepatic abscesses in a renal transplant recipient

Mycobacterium kansasii is the second most frequent cause of non-tuberculous mycobacterial disease in the United States after Mycobacterium avium complex. While primarily it is a pulmonary disease, extrapulmonary manifestations are common. This case report describes a recent renal transplant recipient with disseminated M. kansasii infection presenting with hepatic abscesses, with discussion of clinical management issues and strategies, and a review of the literature.