J. Weinkauf

Why do Some Countries Publish More Than Others? An International Comparison of Research Funding, English Proficiency and Publication Output in Highly Ranked General Medical Journals

National factor(s) influencing publication output in the highest ranked medical journals are largely unknown. We sought to examine the relationship between national research funding and English proficiency on publication output. We identified all original research articles appearing in the five highest ranked general medical journals between 1997 and 2001. Using the country of the corresponding author as the source nation for each article, we determined a standardized publication rate across developed nations. We used multiple regression techniques to determine the influence of national expenditures on research and scores from the Test of English as a Foreign Language (TOEFL), a surrogate for English proficiency, on publication output. There was a significant relationship of national spending on research and TOEFL scores to publication output of developed countries (p= 0.04; p < 0.01, respectively). These two variables explained approximately 71.5% of the variation in publication rate across developed nations around the world (R= 0.85; p < 0.01). Normalized for population size, English-speaking nations and certain northern European countries such as Denmark, The Netherlands, Switzerland, and Sweden had the highest rate of publication in the five highest ranked general medical journals, while Asian countries had generally low rates of publication. Research spending and English proficiency were strongly associated with publication output in the highest ranked general medical journals. While these data cannot be considered definitive due to their observational nature, they do suggest that for English-language medical journals, research funding and English proficiency may be important determinants of publication.

An international survey of cytomegalovirus management practices in lung transplantation.

Background. Cytomegalovirus (CMV) is an important infection in lung transplant recipients. Center-to-center variation in preventive and treatment strategies is unknown. Methods. An electronic survey was sent to 102 lung transplant programs registered with the International Society of Heart and Lung Transplantation and United Network for Organ Sharing. Results. Fifty-nine (58%) programs responded to the survey. For CMV prevention (D+/R−), 56 of the 59 (94.9%) programs used prophylaxis and two (3.4%) of them used preemptive therapy. For R+ patients, 86.4% used prophylaxis and 13.6% used preemptive strategy. Duration of prophylaxis was extremely variable ranging from 3 months to indefinite. Adjunctive prophylactic strategies included routine viral monitoring (51% D+/R−; 44% R+) and CMV immunoglobulin (32% D+/R−; 14% R+). The medication used for prophylaxis was valganciclovir with approximately half starting with intravenous ganciclovir. 9 of the 59 (15.2%) centers reported using specific CMV prophylaxis in D−/R− patients. Methods for viral monitoring included peripheral blood polymerase chain reaction, antigenemia, bronchoalveolar lavage viral culture, and bronchoalveolar lavage polymerase chain reaction. For treatment of CMV viremia, valganciclovir or intravenous ganciclovir were used. A total of 47.5% of centers routinely decreased immunosuppression at the time of viremia. Secondary antiviral prophylaxis was used routinely by 36 of the 59 (61%) centers. Conclusions. Although prophylaxis is the most commonly used preventive strategy, significant variation exists in the way it is implemented. Specifically, duration of prophylaxis is extremely variable. Uniform international guidelines would be of value in this population.

Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients

BACKGROUND In this study we compared the immunogenicity of influenza vaccine administered intradermally to the standard intramuscular vaccination in lung transplant recipients. METHODS Patients were randomized to receive the trivalent inactivated seasonal 2008-9 influenza vaccine containing either 6 μg (intradermal) or 15 μg (intramuscular) of hemagglutinin per viral strain. Immunogenicity was assessed by measurement of geometric mean titer of antibodies using the hemagglutination-inhibition (HI) assay. Vaccine response was defined as a 4-fold or higher increase of antibody titers to at least one vaccine antigen. RESULTS Eighty-five patients received either the intradermal (n = 41) or intramuscular (n = 44) vaccine. Vaccine response was seen in 6 of 41 patients (14.6%) in the intradermal vs 8 of 43 (18.6%) in the intramuscular group (p = 0.77). Seroprotection (HI ≥ 1:32) was 39% for H1N1, 83% for H3N2 and 29% for B strain in the intradermal group vs 28% for H1N1, 98% for H3N2 and 58% for B strain in the intramuscular group (p = 0.36 for H1N1, p = 0.02 for H3N2, p < 0.01 for B). Mild adverse events were seen in 44% of patients in the intradermal group and 34% in the intramuscular group (p = 0.38). CONCLUSIONS Immunogenicity of the 2008-9 influenza vaccine given intradermally or intramuscularly was overall poor in lung transplant recipients. Novel strategies for influenza vaccination in this population are needed.

Emergence of Aspergillus calidoustus infection in the era of posttransplantation azole prophylaxis.

Background Universal antifungal prophylaxis with azoles is commonly used after lung transplantation. We noted an increase in isolates of Aspergillus calidoustus in our transplant population and hypothesized that increasing azole use (universal prophylaxis since 2008) may be promoting this infection. Methods Clinical and microbiologic data for A. calidoustus cases from 2008 to 2011 were extracted from chart review. For lung transplant patients, a case-control study was performed to determine risk factors, and incidence rates were calculated. Results From 2008 to 2011, we identified seven organ transplant recipients and one hematopoietic stem-cell transplant patient with positive A. calidoustus culture results in bronchoalveolar lavage at a median of 13 months after transplantation (interquartile range, 4–39 months). Chest computed tomographic scan was consistent with fungal infection in six of eight patients, and the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria classified these as “probable” invasive aspergillosis. In the case-control study, there were no differences in immunosuppression, number of respiratory samples taken, length of intensive care unit stay, or rejection rates. Of controls, 33.3% received third-generation azole prophylaxis compared with 83.3% of cases (P=0.13). However, median duration of exposure was greater in cases than in controls (3 vs. 0 months, P=0.045). Fungal minimum inhibitory concentration for voriconazole was 4 µg/mL or greater for six of eight cases. Incidence rates in lung transplants showed an increase of A. calidoustus (0/1000 vs. 11.3/1000 patient-years in 2006–2007 and 2008–2011, respectively; P=0.018), whereas Aspergillus fumigatus cases decreased (73.9/1000 vs. 49.0/1000 patient-years, P=0.0066). Conclusions Pulmonary A. calidoustus seems to be an emerging pathogen mainly in lung transplants. We suggest that third-generation azole use reduced the incidence of A. fumigatus, but the incidence of A. calidoustus, an azole-resistant fungus, was increased.

Methicillin-resistant Staphylococcus aureus Infection After Lung Transplantation: 5-year Review of Clinical and Molecular Epidemiology

BACKGROUND Data on the epidemiology of MRSA infection in lung transplantation is limited. METHODS We performed a 5-year retrospective study to assess the incidence and microbiologic and clinical characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infection in a cohort of 163 lung transplant recipients. RESULTS Seventeen patients with MRSA colonization and/or infection were identified, for a calculated incidence rate of 76.1 cases per 1,000 transplanted-years. Pulsed-field gel electrophoresis identified 3 different distinct MRSA profiles, all of them consistent with hospital-associated MRSA infection. CONCLUSION Despite negative polymerase chain reaction (PCR) for the virulence factor Panton-Valentine leukocidin, MRSA infections resulted in significant disease and morbidity.

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BackgroundArteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.MethodsWe reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients.ResultsThirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression.ConclusionsThis first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.

Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: a population-based cohort study

BACKGROUND Acute kidney injury (AKI) is a serious complication following lung transplantation (LTx). We aimed to describe the incidence and outcomes associated with AKI following LTx. METHODS A retrospective population-based cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post-operative days. Secondary outcomes included risk factors, utilization of renal replacement therapy (RRT), occurrence of post-operative complications, mortality and kidney recovery. RESULTS Of 445 LTx recipients included, AKI occurred in 306 (68.8%), with severity classified as Stage I in 38.9% (n = 173), Stage II in 17.5% (n = 78) and Stage III in 12.4% (n = 55). RRT was received by 36 (8.1%). Factors associated with AKI included longer duration of cardiopulmonary bypass [per minute, odds ratio (OR) 1.003; 95% confidence interval (CI), 1.001-1.006; P = 0.02], and mechanical ventilation [per hour (log-transformed), OR 5.30; 95% CI, 3.04-9.24; P < 0.001], and use of cyclosporine (OR 2.03; 95% CI, 1.13-3.64; P = 0.02). In-hospital and 1-year mortality were significantly higher in those with AKI compared with no AKI (7.2 versus 0%; adjusted P = 0.001; 14.4 versus 5.0%; adjusted P = 0.02, respectively). At 3 months, those with AKI had greater sustained loss of kidney function compared with no AKI [estimated glomerular filtration rate, mean (SD): 68.9 (25.7) versus 75.3 (22.1) mL/min/1.73 m(2), P = 0.01]. CONCLUSIONS By the KDIGO definition, AKI occurred in two-thirds of patients following LTx. AKI portended greater risk of death and loss of kidney function.

Risk factors and outcomes for the development of malignancy in lung and heart-lung transplant recipients.

BACKGROUND Many factors may limit survival from lung and heartlung transplantation, including malignancy. OBJECTIVE To investigate factors associated with the development of malignancy following transplantation and its effect on survival by retrospectively reviewing a population of lung transplant recipients. METHODS Data from 342 consecutive lung transplant patients were collected. Results were analyzed by fitting variables into a multivariate logistic regression model predicting the development of post-transplant malignancies. Covariates were selected based on crude associations that reached a level of significance at P ≤ 0.10. Length of survival was analyzed using the Kaplan-Meier method. RESULTS Fifty-eight subjects developed post-transplant malignancies, which were the cause of death of 14 patients. Twenty-one patients had a pretransplant malignancy, of whom six developed a malignancy posttransplant--of these, two were fatal recurrences. No risk factors were significantly associated with all forms of post-transplant malignancy. When adjusted for age at transplantation and donor smoking history, Epstein-Barr virus seropositivity at the time of transplant was significantly associated with a reduced risk of a post-transplant lymphoproliferative disorder (OR 0.17; 95% CI 0.05 to 0.59). The median survival time in individuals without a post-transplant malignancy was significantly shorter than in those with a post-transplant malignancy (P = 0.018 Wilcoxon [Breslow]). This may be secondary to the length of time required to develop malignancy and the fact that not all malignancies that developed were fatal. The median time to develop malignancy was greater than two years. In addition, the 14 patients who died as a result of their malignancy had a significantly shorter survival time than the 44 who died because of nonmalignant causes (P < 0.001). CONCLUSIONS Malignancy was not associated with an overall decrease in survival time when compared with those who did not develop a malignancy. Risk factors specific for the development of malignancies remain difficult to specify.

Outcomes of Lung Transplantation in Recipients with Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV‐positive, compared to 443 HCV‐negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1‐, 3‐, and 5‐year survival were similar in HCV RNA–positive versus ‐negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long‐term follow‐up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon‐free HCV therapies this should not be a barrier to LuTx.

The use of patient-reported outcomes becomes standard practice in the routine clinical care of lung–heart transplant patients

Objective: To assess the use of patient-reported outcome (PROs) measures in the routine clinical care of lung–heart transplant patients. We assessed whether the addition of PROs in routine clinical care affected the duration of the consultation and patient’s and clinician’s views. Method: Consecutive lung–heart transplant patients visiting the outpatient clinic, University of Alberta Hospital, completed the Chronic Respiratory Questionnaire (CRQ) and the Health Utilities Index (HUI) on touchscreen computers. Information on the patient’s responses was made available to the members of the transplant team prior to the encounter with the patient. The duration of clinical encounters was noted. At the end of every visit, clinicians completed a questionnaire on the usefulness of having PRO information available. After 6 months patients completed a survey of their experiences. Results: The final patient sample consisted of 172 patients with a mean (SD) age of 52 (13.3) years old; 47% were female; 68% were organ recipients and 32% candidates. The transplant team, comprising four pulmunologists, two nurses, and one pharmacist had an average of 9 years of practical experience in pulmunology. The mean duration of patient–clinician encounters in minutes was 15.15 (4.52). Ninety-eight percent of patients indicated that they would be happy to complete the CRQ and HUI at every clinic visit. Ninety-one percent of the assessments completed by clinicians showed complete satisfaction with the use of PROs in routine practice. Further, the clinicians developed guidelines for the use of PRO information in clinical practice. Conclusions: The incorporation of PRO measures in the routine clinical care of lung–heart transplant patients resulted in a reduction of the duration of patient–clinician encounters. The experience was well accepted by patients and clinicians. We conclude that the routine use of PROs in lung–heart transplant patients has become standard practice.