Preemptive Management Research Articles

Compartment syndromes from head to toe

Compartment syndrome is defined as the dysfunction of organs/tissues within the compartment due to limited blood supply caused by increased pressure within the compartment. The aim of this article is to introduce and discuss acute compartment syndromes that are essential for critical care physicians to recognize and manage. Various pathophysiological mechanisms (ischemia-reperfusion syndrome, direct trauma, localized bleeding) could lead to increased compartmental pressure and decreased blood flow through the intracompartmental capillaries. Although compartment syndromes are described in virtually all body regions, the etiology, diagnosis, treatment, and prevention are best characterized for three key body regions (extremity, abdominal, and thoracic compartment syndromes). Compartment syndromes can be classified as either primary (pathology/injury is within the compartment) or secondary (no primary pathology or injury within the compartment), and based on the etiology (e.g., trauma, burn, sepsis). A recently described phenomenon is the "multiple" compartment syndrome or "poly"-compartment syndrome, which is usually a complication of a severe shock and massive resuscitation. The prevention of compartment syndromes is based on preemptive open management of compartments (primary syndromes) in high-risk patients and/or careful fluid resuscitation (both primary and secondary syndromes) to limit interstitial swelling.

When Treating Cancer, Please Don't Forget Hepatitis B

Four cases highlighting the reactivation of hepatitis B virus during chemotherapy are presented and the current data and guidelines for pre-emptive management are reviewed.

The evolution of aortic root surgery for Marfan syndrome

In the development of a complex process with multiple iterations, a point may be reached when the next best step is simplification. The pre-emptive management of the Marfan aortic root, which has the single goal of preventing fatal dissection, may be an example. In the light of our report in Interactive CardioVascular and Thoracic Surgery w1x is it time to ask if, with progress in imaging and computer aided design, we might be approaching a point where simplification is the next best step in the elective management of the aortic root in the early uncomplicated Marfan patient? Pepper et al. report the technical realisation of a concept of individualised external aortic root support (EARS) w1x which was proposed and developed by the design engineer Golesworthy w2x. He inherited and has expressed the Marfan gene with all of its characteristic manifestations including dilatation of his aortic root. While undergoing regular echo measurements to see if the aortic root was enlarging, to the point where he met existing criteria for a root replacement, he instigated a radical rethink on our surgical approach. While aware of the work of the surgeon Robicsek and the engineer Thubrikar w3x, Golesworthy postulated that surgeons had thus far failed to take advantage of the techniques of computer aided design. He proposed that we use the very high-resolution spatial data made available by modern imaging to make an exact, customised support for the Marfan aortic root. The anatomical requirements were explored in collaboration with Treasure et al. w4x and Golesworthy himself was the recipient of the first implant w2x. The Bentall operation can be performed at low risk in expert hands and valve-sparing versions, with all their advantages, are now available w5, 6x. During training in the 1970s the situation was very different. The Bentall operation had not long been described w7x and aortic root surgery was a technical challenge, not to be undertaken unless the clinical indications were compelling – but for Marfan patients the very high risk of fatal dissection at young age constituted a compelling argument. For a young surgeon in

Prophylaxis Versus a Preemptive Approach for Invasive Aspergillosis

Difficulty in making an early diagnosis of invasive aspergillosis and consequent poor clinical outcome have led to prophylactic and preemptive management strategies in patients at high risk. Classic high-risk populations include patients with chemotherapy-induced prolonged neutropenia in the setting of acute leukemia and allogeneic hematopoietic stem cell recipients with graft-versus-host disease. Prophylactic mode involves antifungal administration throughout the “at risk” period to prevent infection; published studies with posaconazole and to a much lesser extent, itraconazole, are of promise. However, many drawbacks of these triazoles preclude their liberal use. A preemptive approach involves serial screening of patients with the fungal biomarker, serum Aspergillus galactomannan, to identify early infection; this strategy may be initiated at the onset of the high-risk period or when there are clinical features suggestive of infection. Limited data available with this strategy in the neutropenic population are somewhat encouraging. Clearly, more refined diagnostic tools, improved “quantification” of risk for invasive aspergillosis in different subsets of patients, and direct comparative studies of the two strategies in different settings are needed. At present, prophylaxis against invasive aspergillosis with mold-active azoles may be reserved for those at the highest risk; for those at intermediate risk, prophylaxis with a yeast-active drug combined with the preemptive screening strategy is prudent.

Economic analysis of angiography and preemptive angioplasty to prevent hemodialysis‐access thrombosis

We sought to determine the economic value of early angiography and prophylactic angioplasty to prevent hemodialysis-access thrombosis. End stage renal disease consumes more than 6% of the Medicare budget. There is a need to understand the financial impact of each component of care. We conducted an observational economic analysis of a closed cohort of 818 hemodialysis patients, of whom 560 were referred for 1437 consecutive radiographic procedures during an 8-year period. Patient-level, bottom-up microcosting methods provided supply and personnel costs before and after expansion of an angiographic referral program. The rate of referral for malfunctioning but nonthrombosed hemodialysis accesses increased from 18.8 +/- 8.8 to 48.3 +/- 11.9 angiographic procedures per 100 patient-years (P < 0.001), which was associated with a decline in access thrombosis from 27.6 to 22.0 events per 100 patient-years (P = 0.029) and a net cost of $34,586 per 100 patient-years. The incremental cost-effectiveness ratio for invasive surveillance was $6,177 per thrombosis event avoided. The angiographic program expanded at the same time that the proportion of autogenous fistulas increased from 28.3% +/- 11.3% to 59.7% +/- 10.7% of total referrals (P = 0.0001). On multivariable logistic regression analysis, the expanded angiography program (P = 0.001) and the proportion of autogenous fistulas (P = 0.0001) were both independently associated with the reduction in access thrombosis. Given the incremental costs and the relatively modest benefits in preventing access thrombosis, preemptive angiographic management may represent a less efficient use of healthcare resources than increasing the number of patients with autogenous fistulas. (c) 2009 Wiley-Liss, Inc.

Patterns of Abies cephalonica seedling recruitment in Mount Aenos National Park, Cephalonia, Greece

Patterns of Abies cephalonica Loudon seedling recruitment at its westernmost geographical limit (western Greece), were studied by monitoring their emergence, survival, and establishment for up to four years in the microhabitats to which seeds are dispersed. Seedlings were monitored on 200 permanent sampling plots established in 11 different locations covering the entire strictly protected Mount Aenos National Park (Cephalonia). Annual seedling mortality rate was estimated in relation to habitat characteristics as well as to their number of cotyledons. A. cephalonica presented the typical behaviour of a masting species in the number of seedlings produced over the four years of study. Of the habitat characteristics studied, ground cover, elevation, soil depth, slope and canopy openness were the main parameters that classified seedling habitat with respect to their emergence. Seedling survival was higher in years of low seedling production. Seedlings with higher cotyledon numbers exhibited higher survival. Our data indicate that A. cephalonica is characterized by remarkable reproductive plasticity, which is expressed in the number of seedlings produced each year and those surviving with respect to its habitat characteristics. Preserving the species implies preserving its habitat. In this sense, Mount Aenos National Park may be the most important protected area for the endemic fir in view of preserving its integrity through pre-emptive management, in the light of current and future threats.

Preemptive Management of Epstein-Barr Virus Reactivation After Hematopoietic Stem-Cell Transplantation

Epstein-Barr virus (EBV) reactivation after hematopoietic stem-cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Because viral load after transplantation is correlated with PTLD occurrence, we developed a preemptive attitude based on polymerase chain reaction (PCR)-guided rituximab administration. We monitored 115 transplant patients with a quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for treatment initiation were a single PCR above 40,000 DNA genome copies per milliliter (gCop/mL) or two rising values above 10,000 gCop/mL. Weekly rituximab infusion at the dose of 375 mg/m was administered until negative PCR results were available. We evaluated the incidence of EBV reactivation and PTLD development. Nineteen patients (16.5%) met the criteria for treatment. Incidence of reactivation was the same in high-risk and standard-risk patients (12 vs. 7, P=0.38). One patient developed PTLD after discontinuation of therapy due to a serious adverse event. No other serious adverse events were noticed. Viral load disappeared after a median of three cycles of therapy, and weekly monitoring allowed prompt intervention. No PTLD-related death was observed, all-cause mortality in the treated population was 68%. Our PCR-guided and rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic stem-cell transplantation is feasible but probably overtreated patients. Prospective trials are strongly needed, they should use uniform PCR techniques and consider higher threshold values for treatment initiation.

Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age <or=40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care.

The effect of host structure on the distribution and abundance of the island sugarcane planthopper, Eumetopina flavipes Muir, vector of Ramu stunt disease of sugarcane

The island sugarcane planthopper, Eumetopina flavipes Muir, is the only known vector for Ramu stunt disease of sugarcane. This study examined the relationship between host plant distribution and abundance, and E. flavipes distribution, abundance and levels of population connectivity in Papua New Guinea (PNG), the Torres Strait (TS) and northern peninsula area (NPA) of Australia, as a first step in establishing E. flavipes invasion potential through the TS/NPA. Results show that E. flavipes utilises a wide range of Saccharum host species in PNG and that the occupation rates and abundances differed significantly among host types. For hosts in common, the proportion of plants occupied in PNG was significantly greater than in TS/NPA. This is likely the result of greater overall host density and connectivity in PNG. E. flavipes abundance per plant did not differ significantly between the two regions suggesting a possible plant-specific abundance and/or dispersal threshold independent of location. Whilst E. flavipes presence and persistence was highly variable at some TS/NPA locations, large and stable infestations occurred down the western edge of the TS archipelago. These populations appear to link PNG to the NPA and offer a potential incursion route for Ramu stunt disease. The stability of these populations appears to be associated with the availability and persistence of host material, which in turn is significantly affected by variation in cultivation practices. In the TS/NPA, implementation of pre-emptive management of E. flavipes via cultivation techniques, such as simultaneous tip-pruning, may be an effective means of control for the pest, and would be simpler and preferable to the direct management of Ramu stunt disease should it be detected in the TS/NPA.

Management of hepatitis B reactivation in patients with lupus nephritis

Hepatitis B is endemic in many Asian countries and immunosuppression may precipitate hepatitic flare. There is little data on the treatment of hepatitis B in patients with systemic lupus erythematosus. We monitored serial transaminase and HBV DNA levels in our HBsAg-positive patients with a history of lupus nephritis and instituted anti-viral treatment in patients who showed virological reactivation. This retrospective pilot study reports the data with this pre-emptive management strategy. Amongst 228 patients with lupus nephritis, eight (3.51%) were HBsAg-positive and five had received Lamivudine treatment for hepatitis B. In two patients the virological flares were preceded by lupus flares that necessitated an increase in immunosuppressive treatment. Median HBV DNA level was 1.9 x 10(7) copies/mL (range 1.2 x 10(4)-1.0 x 10(9) copies/mL) at baseline, and it decreased by 2-5 logs after treatment. Four patients had abnormal transaminase levels at baseline, with mean alanine aminotransferase at 125.0 +/- 67.4 U/L, and all achieved normalisation after 3-24 months (median 13 months) of treatment. Discontinuation of Lamivudine treatment was attempted in three patients after 9-15 months. In one patient treatment was recommenced because of virological flare. For the remaining two patients in whom treatment was not interrupted, one showed sustained viral suppression and one developed drug resistance. All antiviral treatments were well-tolerated. These results indicate the importance of serial monitoring of HBV DNA and transaminase levels, and prompt anti-viral therapy, in the management of HBsAg-positive lupus patients. Also, it may be feasible to discontinue treatment in stable patients to avoid the selection of drug-resistant variants.

Assessment, Physiological Monitoring, and Consequences of Inadequately Treated Acute Pain

Postoperative pain is a major health care issue. Several factors have contributed to inadequate postoperative pain control, including a lack of understanding of preemptive pain management strategies, mistaken beliefs and expectations of patients, inconsistencies in pain assessment practices, use of as-needed analgesics that patients must request, and lack of analgesic regimens that account for interindividual differences and requirements. Untreated acute pain has the potential to produce acute neurohumoral changes, neuronal remodeling, and long-lasting psychologic and emotional distress and may lead to prolonged chronic pain states. To effectively manage postoperative pain, nurses must be able to adequately assess pain severity in diverse patient populations, understand how to monitor physiologic changes associated with pain and its treatment, be prepared to address the psychosocial experiences accompanying pain, and know the consequences of inadequate analgesia. It is important for nurses to be aware of relevant research and evidence-based guidelines that are available to guide pain assessments and patient monitoring practices.

Assessment, Physiological Monitoring, and Consequences of Inadequately Treated Acute Pain

Postoperative pain is a major health care issue. Several factors have contributed to inadequate postoperative pain control, including a lack of understanding of preemptive pain management strategies, mistaken beliefs and expectations of patients, inconsistencies in pain assessment practices, use of as-needed analgesics that patients must request, and lack of analgesic regimens that account for inter-individual differences and requirements. Untreated acute pain has the potential to produce acute neurohumoral changes, neuronal remodeling, and long-lasting psychological and emotional distress, and may lead to prolonged chronic pain states. To effectively manage postoperative pain, nurses must be able to adequately assess pain severity in diverse patient populations, understand how to monitor physiological changes associated with pain and its treatment, be prepared to address the psychosocial experiences accompanying pain, and know the consequences of inadequate analgesia. It is important for nurses to be aware of relevant research and evidence-based guidelines that are available to guide pain assessments and patient-monitoring practices.

Pre-emptive management of polyomavirus BK in pediatric kidney transplant recipients

Pre-emptive management of polyomavirus BK in pediatric kidney transplant recipients

Preemptive Management of Epstein-Barr Virus Reactivation after Hematopoietic Stem Cell Transplantation.

Introduction - Epstein-Barr virus (EBV) reactivation after hematopoietic stem cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Transplants using T-cell-depleted graft or antithymocyte globulin are considered as high-risk. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Since viral load after transplantation is correlated to PTLD occurrence, we have developed a preemptive attitude based on PCR-guided rituximab administration.Methods - We monitored 115 transplant patients with a quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for treatment initiation were a single PCR above 40,000 DNA genome copies per litre (gCop/L) or two rising values above 10,000 gCop/L. Weekly rituximab infusion at the dose of 375 mg/m2 was administered until negative PCR results were available. We evaluated incidence of EBV reactivation and PTLD development.Results - 19 patients (16.5%) met the criteria for treatment. Incidence of reactivation was the same in high-risk and standard-risk patients (12 vs 7, p=0.38). One patient developed PTLD after discontinuation of therapy due to a serious adverse event. No other serious adverse events were noticed. Viral load disappeared after a median of 3 cycles of therapy and weekly monitoring allowed prompt intervention. No PTLD-related death was observed, all-cause mortality in the treated population was 68%.Conclusions - Our PCR-guided and rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic stem cell transplantation is safe and feasible but probably overtreated patients. Prospective trials should concentrate on high-risk patients, use uniform PCR techniques, and consider higher threshold values for treatment initiation.Characteristics of transplant population (n=115)Age (median and range)39 (15–69)Diagnosis AML31 ALL17 NHL15 CML12 MM11 MDS10 CLL6 AA4 Others9Type of transplant Myeloablative Sib donor29 Myeloablative MUD12 Nonmyeloablative Sib donor32 Nonmyeloablative MUD9 Haploidentical33Alive32 (28%)AML : acute myeloid leukemia - ALL : acute lymphoblastic leukemia - NHL : non Hodgkin's lymphoma - CML : chronic myelogenous leukemia - MM : multiple myeloma - MDS : myelodysplastic syndrome - CLL : chronic lymphocytic leukemia - AA : aplastic anemia - Sib donor : HLA-matched sibling donor - MUD : HLA-matched unrelated donorCharacteristics of treated patients (n=19)Age (median)30 (18–62)DiagnosisAML4ALL6NHL0CML4MM0MDS1CLL1AA1Others2Type of transplantMyeloablative Sib donor6Myeloablative MUD3Nonmyeloablative Sib donor4Nonmyeloablative MUD0Haploidentical6TCD/ATG12EBV serologyD+/R+17D−/R−0D+/R−1D−/R+1Immunosuppressive drugsCnl alone2steroids alone1Cnl-steroids5Cnl-MMF-steroids4Others1None0GVHDAcute9Chronic2Alive6 (32%)Cause of deathrelapse of malignancy4GVHD4Infection4Others1AML : acute myeloid leukemia - ALL : acute lymphoblastic leukemia - NHL : non Hodgkin's lymphoma - CML : chronic myelogenous leukemia - MM : multiple myeloma - MDS : myelodysplastic syndrome - CLL : chronic lymphocytic leukemia - AA : aplastic anemia - Sib donor : HLA-matched sibling donor - MUD : HLA-matched unrelated donor - TCD : ex vivo T cell depletion - ATG : antithymocyte globulin administration - D/R : donor / recipient serology - Cnl : calcineurin inhibitor (cyclosporin, tacrolimus) - MMF : mycophenolate mofetil

Environmental sustainability and land reform in South Africa: A neglected dimension

Despite supportive policy frameworks and increased environmental awareness, a growing body of evidence indicates that environmental sustainability is not central to planning and decision-making processes in land reform in South Africa. Increasing pressures on government to meet land reform targets, cumbersome and often inappropriate environmental assessment procedures, and a confusing multitude of laws all contribute to neglect of long-term environmental sustainability considerations in land reform. This is exacerbated by poor recognition of resource rights, a lack of proactive and pre-emptive environmental management plans, and insufficient implementation capacity. This paper argues that the early incorporation of environmental sustainability issues in pre-settlement and post-settlement land reform planning processes could significantly improve the environmental, social and economic outcomes of these projects. A simple, participant-driven environmental sustainability assessment tool is proposed to achieve these environmental and developmental goals.

Analysis of Wegener’s Granulomatosis Responses to Rituximab: Current Evidence and Therapeutic Prospects

Available data on small numbers of patients with refractory and/or relapsing Wegener's granulomatosis support very good overall outcomes with rituximab, an anti-CD20 biotherapy targeting B cells, in combination with ongoing immunosuppressants, apparently independently of antineutrophil cytoplasm antibody (ANCA) status. However, clearly dissociated responses were observed, with constitutional and vasculitis-related symptoms often achieving complete responses within days or weeks, and granulomatous-related manifestations regressing more slowly over a few weeks to several months or not at all, particularly for orbital pseudotumors. Tolerance was good with few side effects, and when relapses occurred, more often after 12 months, a second or even a third rituximab cycle was almost always able to obtain another complete remission. Randomized trials are needed to define rituximab's best place, compared to cyclophosphamide, in initial and maintenance regimens; to determine optimally combined drugs, considering the various responses of granulomatous-related manifestations; and to delineate the role of circulating B-cell monitoring for pre-emptive management decisions. This promising biotherapy opens the way for other therapeutic agents targeting B lymphocytes and to improve our understanding of the pathophysiology of ANCA-associated vasculitis.

Postoperative Pain Control: Preemptive Management

Strategies for improving outcomes of surgical procedures have been investigated, specifically in regards to post operative pain. The extraction of impacted third molars is an operative procedure known to induce a significant amount of pain and discomfort. Techniques to improve these outcomes include the potential for the pre-emptive management of the pain to prevent the expected peripheral and central nociceptive impulses.

The Effect of Preemptive Analgesics on Third Molar Outcomes

Control of pain following elective but necessary surgical removal of third molars for many is an afterthought, or managed with a “cookbook” management scheme of simply writing a prescription for a large number of combination analgesic tablets or capsules (acetaminophen plus an opioid). This approach spawns multiple concerns and problems including opioid overdose, dependency and addiction, liver failure, and bleeding disorders. There has been significant research addressing preemptive pain management to minimize post operative pain. Reducing or preventing pain however with current pharmacologic agents and accepted technique may have some adverse impact on the healing process. A consistent yet alterable pain management technique is obtainable for improvement of patient satisfaction with the procedure experience. Recent research regarding timing of analgesic dosing, use of modalities that effect pain control during sedation or general anesthesia, and efficacy associated with the use of local anesthesia agents will be presented.

Using genetic variation to optimize nutritional preemption.

One of the promises of nutritional genomics is a set of dietary recommendations that leverage our understanding of nutrient-gene interaction in the preemptive dietary management of complex chronic diseases. Whether nutritional genomics can deliver on this promise is a matter of debate and controversy. Although nutritional genomics is often viewed as an extension of pharmacogenomics, the pharmacogenomics paradigm is a disease-centric reductionistic model that overshadows both the complexities and opportunities to be leveraged in preemptive nutritional pharmacology. Moreover, the pharmacogenomics model tends to set clinical expectations that nutritional genomics may not be able to achieve. The biological boundaries of nutritional pharmacology are being tested in many areas of preventive medicine such as cardiovascular disease and cancer. In this regard, the lessons learned in one disease may be germane to the other. Recent results from the Vitamin Intervention for Stroke Prevention (VISP), the Norwegian Vitamin (NORVIT), and the Heart Outcomes Prevention Evaluation (HOPE) 2 trials underscore the incertitude of translating epidemiologic data into preemptive nutritional guidance. Moving ahead, the genetic determinism of the nutrigenomic model needs to take on a more holistic and phenotypic focus. To the extent this can be done, preemptive nutrition may one day become a safe and practical reality.

Clinical utility of CMV early and late transcript detection with NASBA in bronchoalveolar lavages

Background Cytomegalovirus (CMV) infection can cause severe disease in immunocompromised individuals, with CMV pneumonia, most commonly seen in lung or bone marrow transplant recipients, carrying a particularly high fatality rate. Early and accurate diagnosis of CMV pneumonia is therefore critical. Objectives Current diagnostic tests for CMV pneumonia in bronchoalveolar lavage (BAL) specimens are either insensitive or poor prognostic indicators of disease. We therefore examined nucleic acid sequence-based amplification (NASBA) assays for CMV transcripts in BAL for the prediction of CMV pneumonia and associated diseases. Study design A total of 220 BAL specimens from lung transplant recipients and other patients with suspected viral pneumonia were studied. Ninety-nine samples had previously tested positive for CMV by shell vial (SV) culture, while the other 121 had tested negative. All specimens were assayed for CMV pp67 and immediate early (IE) transcripts by NASBA. Results were correlated with evidence of concurrent or subsequent CMV pneumonia, rejection, and infection with other microbes. Results From a total of 220 BAL specimens, 27 tested positive for pp67 mRNA, 25 tested positive for IE mRNA, and 17 tested positive for both. Only 10 specimens tested positive for CMV by either or both NASBA assays while testing negative by SV assay. However, 74 specimens were SV positive but negative in both NASBA assays. Detection of CMV by any of the three methods was associated with an increased prevalence of pneumonia (i.e., pulmonary interstitial inflammation with radiographic or clinical evidence of lung injury), but not with pulmonary CMV pathology. Detection of CMV by SV was associated with moderate to severe graft rejection. There was no evidence of increased bacterial or fungal pulmonary infections associated with a positive CMV result by any of the three assays. Conclusions Detection of either CMV pp67 or IE mRNA transcripts by NASBA in BAL specimens can occasionally identify CMV infections that are negative by conventional shell vial culture, but does not have sufficient sensitivity or positive predictive value to be employed routinely for pre emptive management of pulmonary CMV disease in transplant recipients.