Invasive aspergillosis in a renal transplant recipient successfully treated with interferon-gamma.

Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.

The use of drug-eluting stents in the management of transplant renal artery stenosis.

Transplant renal artery stenosis (TRAS) is a common occurrence following kidney transplantation with an incidence rate ranging from 6% to 23%. A single-center retrospective study was conducted to examine the use of drug-eluting stents (DES) in eligible patients with hemodynamically significant TRAS. Between March 2008 and January 2011, 12 patients were diagnosed with TRAS with reference vessel diameter measuring <5 mm and underwent endovascular intervention (EVI) with DES placement. TRAS was detected within the first year posttransplantation in a majority of these patients (83%) and manifested as hypertension (100%), allograft dysfunction (100%) and edema (58%). Procedural success rate was 100%. Patients were followed for a mean period of 16 ± 10 months. Blood pressure improved from a mean of 156/82 to 138/73 mmHg at the end of the follow-up period. In 11/12 patients, serum creatinine improved from 3.1 ± 1.3 mg/dL to 2.3 ± 0.5 mg/dL at the end of the follow-up period. TRAS of early onset is readily amenable to EVI with stent placement resulting in improvement in blood pressure control and allograft function.

Uterine leiomyoma causing urinary obstruction of the transplanted kidney.

Obstruction of the ureter as a cause of acute or chronic kidney injury in the transplanted kidney is unusual beyond the perioperative period. We present a case of ureteric obstruction, infection and septicemia caused by a large uterine leiomyoma in a patient 8 years post transplantation. Initial treatment comprised of intravenous fluid and antibiotics followed by urgent drainage of the collecting system. Subsequent hysterectomy resolved the obstruction with resolution of renal failure. In young female kidney transplant recipients, gynecologic causes, although rare, need to be considered as possible etiologies of urinary obstruction and renal dysfunction.

Sirolimus-associated diffuse alveolar hemorrhage in a renal transplant recipient on long-term anticoagulation.

Sirolimus (rapamycin, rapamune) is an effective immunosuppressant that has been widely used in solid organ transplantation. Recently, two disconcerting side effects, namely pulmonary toxicity, usually in the form of interstitial pneumonitis, and the onset of nephrotic range proteinuria, have been recognized. We report the case of a renal transplant recipient who had been on chronic anticoagulation therapy for a mechanical aortic valve, and who developed pulmonary distress necessitating emergent intubation 18 days after starting sirolimus therapy. Open lung biopsy showed diffuse alveolar hemorrhage with fibrin deposits in the alveolar spaces and small bronchi. Urine protein/creatinine ratio at that time was 16.7. Upon discontinuation of sirolimus, alveolar hemorrhage and nephrotic range proteinuria resolved. We suggest that extra vigilance be paid in individuals who are on chronic anticoagulation and who are started on sirolimus.

Delayed renal allograft dysfunction and cystitis associated with human polyomavirus (BK) infection in a renal transplant recipient: a case report and review of literature.

Human polyomavirus type BK (BKV) associated nephritis (BKVAN) has recently emerged as an important cause of renal allograft dysfunction and failure. Early recognition of this entity as a cause of allograft dysfunction is extremely important since misdiagnosis can accelerate graft loss. We report a case of BKVAN that presented with symptoms related to cystitis, and review the risk factors, the diagnostic tools and the approach to treatment of BK virus associated allograft nephropathy.

Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication.

Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis.

Managing material transfer and nutrient flow in an agricultural watershed.

Place-based resource management, such as watershed or ecosystem management, is being promoted to replace the media-focused approach for achieving water quality protection. We monitored the agricultural area of a 740-ha watershed to determine the nature and scale of farm material transfers, N and P balances, and farmer decisions that influenced them. Using field data and farmer interviews we found that 3 of 15 farms, emphasizing hog, dairy, or cash crops with poultry production, accounted for more than 80% of the inputs and outputs of N and P for the 362-ha agricultural area (332 ha of managed cropland and animal facilities). Feed for hogs (38% each of total N and P) and manure applied to fields as part of the cash crop and poultry operation (28 and 38% of total N and P, respectively) were the dominant inputs. No crops grown in the watershed were fed to animals in the watershed and more manure nutrients were applied from animals outside than from those in the watershed. A strategic decision by the hog farmer to begin marketing finished hogs changed the material transfers and nutrient balances more than tactical decisions by other farmers in allocating manure to cropland. Since the components of agricultural production were not all interconnected, the fundamental assumption of place-based management programs is not well-suited to this situation. Alternative approaches to managing the effect of agriculture on water quality should consider the organization of agricultural production and the role of strategic decisions in controlling farm nutrient balances.

Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.

OBJECTIVE: To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes. STUDY DESIGN: Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34. PARTICIPANTS: 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17). RESULTS: Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c) values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA(1c) values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy. CONCLUSION: The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.

Combined medical surgical therapy for pulmonary mucormycosis in a diabetic renal allograft recipient.

Mucormycosis is a rare opportunistic infection that complicates chronic debilitating diseases and immunosuppressed solid-organ transplant recipients. We present a case of life-threatening pulmonary mucormycosis in a diabetic renal allograft recipient who survived with reasonable renal function. Early recognition of this entity and prompt use of bronchoalveolar lavage (BAL) are critical to the outcome. Antifungal therapy combined with early surgical excision of infected, necrotic tissue appears to be the preferred course of action. Judicious withholding of immunosuppressants until fungemia cleared did not jeopardize allograft function.

The desirability of a condition versus the well being and worth of a person.

The desirability of a condition to people who are not in it themselves is only moderately correlated to the experienced well being of people with the condition and hardly correlated at all to the worth of those people. A single score for a health state, of the kind used in QALY calculations, cannot express all these three types of value. The history and current practice of health economics is highly problematic in this respect.

Health state values from multiattribute utility instruments need correction.

Cost-utility analysis uses the quality-adjusted life year (QALY) as a measure of the benefit of health interventions. It presupposes the assignment of utility scores to different states of health on a scale from zero (dead) to unity (healthy). A number of so-called multiattribute utility (MAU) instruments are available for this purpose. Analysts who wish to use MAU instruments in economic evaluations of health programmes and technologies may improve their performance by conducting two different analyses: the first is a conventional cost-utility study, in which the utilities from MAU instruments are used as they stand, and the second is a study in which the utilities are transformed into numbers that also encapsulate concerns for giving priority to the worst off. The term 'cost-value analysis' is used for the latter, broader approach. A figure is offered as a preliminary tool to help conduct the required transformations.

Cost-utility analysis of high-dose melphalan with autologous blood stem cell support vs. melphalan plus prednisone in patients younger than 60 years with multiple myeloma.

We evaluated the costs and the cost utility of high-dose melphalan and autologous stem cell support followed by interferon maintenance relative to conventional treatment with melphalan and prednisone, in patients less than 60 yr of age with multiple myeloma. From March 1994 to July 1997, 274 patients with newly diagnosed, symptomatic multiple myeloma were enrolled in a prospective, non-randomized, population-based, multicenter study to evaluate the treatment with high-dose melphalan and autologous blood stem cell support. Health-related quality-of-life was measured prior to treatment and during follow-up, using the EORTC QLQ-C30 questionnaire. Resource consumption was also recorded prospectively. The intensive treatment yielded a significant increase in median survival time from 44 to 62 months compared to conventionally treated patients. The corresponding gain in quality-adjusted life years (QALY) was found to be 1.2. Cost per QALY gained by the treatment with high-dose melphalan and autologous blood stem cell support was estimated at NOK 249,000 (USD 27,000).

Severity of illness versus expected benefit in societal evaluation of healthcare interventions.

Society's valuation of a healthcare outcome depends not only on the size of the gain in well-being (utility), but also on the severity of the initial condition. This seems to be a major problem with the conventional utility-based QALY approach to outcome evaluation. In particular, QALY calculations based on utilities from multiattribute utility instruments assign too high value to interventions for people with mild and moderate health problems compared with interventions for people with severe and life threatening diseases. Analysts should somehow make corrections for this bias in economic evaluations of healthcare programs.

Human T-cell lymphotropic virus testing of blood donors in Norway: a cost-effect model.

BACKGROUND: Human T-cell lymphotropic virus type I and II (HTLV-I and II) are human retroviruses that can be transmitted by transfusion of whole blood. An HTLV-I infection is associated with adult T-cell leukaemia (ATL) and with tropical spastic paraparesis (TSP). Antibody tests from 5.5 million European blood donors have shown that the HTLV prevalence is low, ranging from 0 to 0.02%. This paper examines costs and effects associated with the intervention of testing all new blood donors for HTLV. METHODS: A mathematical model was used to calculate the number of cases prevented by the intervention. For a given prevalence of HTLV in the blood donor population, the model calculates the number of recipients infected by transfusion, and the number of partners and offspring that will in turn be infected. The model then calculates the number of subjects with disease due to HTLV-I infection and the number of deaths from disease. From these numbers the measures of cost and effect are calculated. RESULTS: Testing all new blood donors for HTLV is calculated to cost US$ 9.2 million per life saved, or US$ 420,000 per quality adjusted life year gained by the intervention, when the HTLV prevalence among donors is 1 per 100,000. When the prevalence among donors is 10 per 100,000 the intervention will cost US$ 0.9 million per life saved, or US$ 41,000 per quality adjusted life year gained. The same analysis shows that testing blood donors for human immunodeficiency virus (HIV) saves money when the HIV prevalence among donors is above 0.7 per 100,000. CONCLUSION: For Norway, studies suggest a willingness to pay to save a statistical life of approximately US$ 1.2 million. The costs fall under this value when the number of infected persons is > or = 8 per 100,000 donors. The results are uncertain because of the uncertainty in HTLV infection and disease parameters.

Improving value measurement in cost-effectiveness analysis.

OBJECTIVE: Before cost-effectiveness analysis (CEA) can fulfill its promise as a tool to guide health care allocation decisions, the method of incorporating societal values into CEA may need to be improved. DESIGN: The study design was a declarative exposition of potential fallacies in the theoretical underpinnings of CEA. Two values held by many people-preferences for giving priority to severely ill patients and preferences to avoid discrimination against people who have limited treatment potential because of disability or chronic illness-that are not currently incorporated into CEA are discussed. CONCLUSIONS: Traditional CEA, through the measurement of quality-adjusted life years (QALYs), is constrained because of a "QALY trap." If, for example, saving the life of a person with paraplegia is equally valuable as saving the life of a person without paraplegia, then current QALY methods force us to conclude that curing paraplegia brings no benefit. Basing cost-effectiveness measurement on societal values rather than QALYs may allow us to better capture public rationing preferences, thereby escaping the QALY trap. CEA can accommodate a wider range of such societal values about fairness in its measurements by amending its methodology.

Cost savings and health losses from reducing inappropriate admissions to a department of internal medicine.

OBJECTIVES: Inappropriate hospital admissions are commonly believed to represent a potential for significant cost reductions. However, this presumes that these patients can be identified before the hospital stay. The present study aimed to investigate to what extent this is possible. METHODS: Consecutive admissions to a department of internal medicine were assessed by two expert panels. One panel predicted the appropriateness of the stays from the information available at admission, while final judgments of appropriateness were made after discharge by the other. RESULTS: The panels correctly classified 88% of the appropriate and 27% of the inappropriate admissions. If the elective admissions predicted to be inappropriate had been excluded, 9% of the costs would have been saved, and 5% of the gain in quality-adjusted life-years lost. The corresponding results for emergency admissions were 14% and 18%. CONCLUSIONS: The savings obtained by excluding admissions predicted to be inappropriate were small relative to the health losses. Programs for reducing inappropriate health care should not be implemented without investigating their effects on both health outcomes and costs.

Epstein-Barr virus infection of renal proximal tubule cells: possible role in chronic interstitial nephritis.

Chronic interstitial nephritis frequently accompanies renal diseases of different etiologies. Far less common is the entity of primary interstitial nephritis wherein the glomerular and vascular structures of the kidney are not the primary focus of the disease process. Using in situ hybridization and the polymerase chain reaction, we detected DNA from the Epstein-Barr Virus (EBV) exclusively in renal tissue of patients with the idiopathic variety of chronic interstitial nephritis. The EBV genome, but not that of cytomegalovirus or adenovirus, was detected primarily in renal proximal tubule cells. Furthermore, the CD21 antigen, which serves as the receptor for EBV in B lymphocytes, was detected by immunocytochemistry primarily on proximal tubule cells and was markedly upregulated in the EBV-infected tissue. Western blot analysis of primary cultures of normal proximal tubule cells identified a 140-kDa protein, confirming the expression of the CD21 antigen. Colocalization experiments using proximal and distal tubule markers confirmed that EBV DNA and the CD21 antigen are found primarily in proximal tubule cells. EBV infection of renal proximal tubular cells may participate in evoking a cellular immune response that results in a damaged renal interstitium.