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PubMed2001

Monozygotic twins discordant for major depression: a preliminary exploration of the role of environmental experiences in the aetiology and course of illness.

BACKGROUND: Genetic effects upon behaviour are pervasive. To what extent are the many correlates of major depression (MD) due to individual-specific environmental experiences versus genetic factors correlated with risk for MD? METHODS: From a population-based twin registry, we identified 72 female monozygotic pairs discordant for a lifetime history of MD and compared the affected and unaffected members on a wide range of putative correlates of MD. RESULTS: The affected twin differed from her unaffected co-twin on many variables, eight of which were maximally discriminating: (i) maternal protectiveness; (ii) conflictual parent-child relationship; (iii) low optimism; (iv) current stressful life events; (v) financial difficulties and a history of (vi) phobia, (vii) nicotine dependence; and (viii) divorce. A cluster analysis suggested three 'environmental pathways' to MD characterized by: (i) childhood vulnerability and anxiety; (ii) acting-out and demoralization; and (iii) interpersonal difficulties. CONCLUSION: Important precursors and sequelae of MD originate in environmental experiences unique to the individual and are not mediated through genetic factors or family-of-origin effects. Such environmental factors cause pervasive differences in monozygotic twins discordant for MD, especially in the areas of interpersonal difficulties, psychopathology, social problems and self-concept. These findings should be interpreted in the context of possible retrospective recall bias and the difficulty of distinguishing risk factors from sequelae in co-twin-control studies.

Adult↗
PubMed2004

Educational research at Johns Hopkins University School of Medicine: a grassroots development.

The Divisions of General Internal Medicine at Johns Hopkins University School of Medicine have been a rich source of educational research. To better understand the facilitators and barriers to educational research within the divisions, the authors reviewed published educational research from the divisions published between 1995-2004 and examined the history, leadership decisions, and sentinel events that have allowed educational scholarship within the divisions to grow. The authors' analysis suggests a grassroots model of programmatic growth that includes a growing cadre of clinician-educator scholars, effective mentorship, a faculty development program, access to learners, access to research expertise, protected time for scholarship, some funding, and an institutional culture that stimulates scholarship. A medical education fellowship was integral to the model; fellows were first authors for 47% of reviewed manuscripts. Extramural funding has helped build an infrastructure that supports educational scholarship; however, only 12% of the publications have had extramural funding. Protected time for faculty is the characteristic of this model most at risk. While there has been a move toward more institutional support of educational research, it is clear that further growth in the educational research program will require noninstitutional resources.

Baltimore↗
PubMed2004

Lipoprotein(a)-associated atherothrombotic risk in hemodialysis patients.

BACKGROUND: Hemodialysis patients show a considerably higher risk of atherothrombotic disease than the general population. We investigated both lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of atherothrombotic events in hemodialysis patients compared with subjects showing a normal kidney function. METHODS: Lp(a) levels and apo(a) isoforms were determined in 118 hemodialysis patients, including 59 with prior atherothrombotic events, and in 182 subjects with normal creatinine clearance, including 82 who experienced a prior atherothrombotic event. RESULTS: Lp(a) levels in hemodialysis patients (median; 20 mg/dl) were higher (p < 0.01) than in age- and sex-matched subjects with normal renal function without a history of atherothrombosis (11.3 mg/dl). Among hemodialysis patients, median Lp(a) levels were higher in subjects with than in those without prior atherothrombosis (34 vs. 15 mg/dl, p < 0.05). In hemodialysis patients and in subjects without nephropathy, the percentage of low-molecular-weight apo(a) phenotypes were significantly higher in patients with than in those without a history of prior atherothrombotic events (56.9% vs. 33.9%, p < 0.05; 62.2% vs. 25%, p < 0.00001,respectively). Stepwise regression analysis indicated that the presence of at least one apo(a) isoform of low molecular weight was an independent predictor of atherothrombosis in hemodialysis patients (p < 0.05). CONCLUSIONS: Elevated Lp(a) plasma levels appear to be associated with atherothrombosis, independent of their origin due to genetic factors or related to the impaired kidney function. Low-molecular-weight apo(a) isoforms are reliable genetic markers of atherothrombosis both in patients with impaired kidney function and in subjects without nephropathy.

Adult↗
PubMed2003

Antiphospholipid antibodies as a risk factor for atherosclerotic events in renal transplant recipients.

BACKGROUND: Epidemiologic studies reported that antiphospholipid antibodies (APAs) were independent predictors of atherosclerotic events. We recently reported a high prevalence of APAs in renal transplant recipients. Nevertheless, the role of APAs on atherosclerotic events has not been prospectively studied in this high-risk population. METHODS: Participants in the study were 324 consecutive renal transplant recipients. Patients were enrolled between January 1996 and May 1998 and followed up until June 2002. RESULTS: The patients were followed for a mean duration of 62 +/- 26 months. Eighty seven (26.8%) patients exhibited APAs. We found a slight, but significant, correlation between total plasma homocysteine (tHcy) concentration and anticardiolipin (ACA) titers (r = 0.26; P = 0.036). Fifty six athersclerotic events (17.2%) occurred in 54 patients. Atherosclerotic events occurred more frequently in patients with APAs (33% vs. 9%; P = 0.0003) and ACAs levels were higher in patients who experienced atherosclerotic events (23.7 +/- 13.1 IU vs. 13.9 +/- 9.4 IU; P = 0.003). APAs were associated with an increased risk of atherosclerotic events (RR, 2.82; 95% CI, 1.17 to 5.31). Cox regression analysis also revealed that age above the median (RR, 5.21; 95% CI, 1.67 to 17.13), a previous history of cardiovascular disease (RR, 3.54; 95% CI, 1.57 to 10.43), hyperhomocysteinemia (RR, 4.01; 95% CI, 1.22 to 14.61), and current smoking (RR, 2.17; 95% CI, 1.01 to 6.72) were risk factors for atherosclerotic events. CONCLUSION: The presence of APAs is an independent cardiovascular risk factor in renal transplant recipients. Prevention trials are necessary to assess the efficacy and safety of anticoagulation therapy in transplant patients with APAs.

Adult↗
PubMed2002

Deficiencies of history taking among medical students.

OBJECTIVE: This study was designed to identify the deficiencies of the history taken by final medical students at the University of Bahr Elghazal, Khartoum, Sudan, during the academic year 2000 through to 2001. METHODS: Throughout the academic year the author observed the students while taking history. Each student was asked to give a fully written case history. I assessed the basic skills of history taking (questioning, facilitation, clarification, jargon use, initiation of interview and keeping to time limits). I also assessed the amount and accuracy of data obtained. The findings were rated on a 3-point scale (good, fair, poor). RESULTS: For the 45 students assessed, the deficiencies of history taking obtained included poor questioning (66.6%), poor facilitation (51.1%), poor clarification (40%), use or acceptance of jargons (42.2%), failure of proper initiation of interview (37.8%), failure of keeping to time limits (33.3%), failure of identification of major symptoms (33.3%), poor analysis of symptoms (53.3%), lack of control of the interview (31.1%), poor elucidation of previous events (48.9%) and poor coverage of social aspects (62.2%). CONCLUSION: The history obtained by our medical students is deficient and they generally lack the basic skills of interviewing. Many factors contribute to this, (namely deficient training, lack of staff and deficit of teaching hospitals). The author discussed possible solutions to remedy the history taking deficiencies.

Clinical Competence↗
PubMed2005

A horse named 'Twilight Sleep': the language of obstetric anaesthesia in 20th century Britain.

Historians of medicine frequently marginalize or completely ignore the importance of linguistics in the development and dissemination of medical theories and clinical techniques, both in professional culture and in society at large. This is particularly true in the history of pain relief in labour, despite the significant role played by popular attitudes to birth and pain relief in the development of clinical services. This paper uses a simple form of citation analysis to examine shifts in the usage of terms related to regional nerve block techniques in The Lancet and The Times from 1900 to 1999. Graphical representations of these data are used to relate changes in the incidence of citations to key events in the 20th century history of obstetric anaesthesia in Britain. A study of the rise and fall of 'twilight sleep' in the early part of the century is used to demonstrate the advantages and disadvantages associated with this approach to medical history. Conclusions from this analysis are used to suggest (tentative) models for the acceptance and diffusion of medical words in professional and popular vocabularies.

Anesthesia, Obstetrical↗
PubMed2006

Characterization of Epstein-Barr virus Type I variants based on linked polymorphism among EBNA3A, -3B, and -3C genes.

Latent Epstein-Barr virus (EBV) nuclear antigens (EBNA)-3A, -3B, and -3C are involved in transcription regulation of both viral and cellular genes. In the present study, we chose functionally important regions within EBNA3A, -3B, and -3C genes with putative tumorigenic potential to investigate natural sequence variations among EBV Type I strains circulating in Europe. Based on the identification of linked EBNA3A, -3B, and -3C sequence patterns, we defined five EBNA3 variants in addition to the B95.8 prototype sequence. Phylogenetic analysis revealed that EBNA3 variant 5, the most diverged from the B95.8 sequence, showed an evolutionary history of intertypic recombination events occurring upstream and downstream of the C-terminus of EBNA3A. The frequency of occurrence of the five newly defined EBNA3 variants was similar for strains causing EBV primary infection or reactivation and was also similar within two of the European areas investigated. In addition, preferential linkages of certain EBNA3 variants to distinct latent membrane protein 1 (LMP1) groups were found to exist. Thus, a combination of more than one polymorphic site in the EBV genome might be involved in determining disease characteristics.

Adolescent↗
PubMed2003

Life course turning points: the effect of grade retention on physical aggression.

Our objective is to advance the life course analytical framework by demonstrating a model for testing two of its tenets. The first is whether the individual's developmental history conditions the response to a turning point event. The second is whether the influence of a major life event upon an individual's developmental course depends upon the timing of the event. We test both propositions in an analysis of the effect of grade retention on a child's trajectory of physical aggression. Our analysis is based on data from a longitudinal study of 1,037 boysfrom schools in the lowest socioeconomic areas in Montreal, Canada. We find clear evidence that a developmental history of physical aggression conditions the child's response to grade retention. The evidence on whether the timing of retention affects this response is less clear.

Adolescent↗
PubMed2000

Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors.

BACKGROUND: The recurrence rate after deep vein thrombosis (DVT) is high and the risk factors for recurrent thromboembolic events have only been investigated on a small scale. OBJECTIVES: To estimate the cumulative incidence of recurrent venous thromboembolic events after a first or a second DVT and to identify possible risk factors for recurrent venous thromboembolism. METHODS: We prospectively followed up 738 consecutive patients with an objectively verified symptomatic DVT for 3.7 to 8.8 years. Medical records and death certificates for all patients were reviewed during follow-up and recurrent DVT and pulmonary embolism were registered. RESULTS: The 5-year cumulative incidence of recurrent venous thromboembolic events was 21.5% (95% confidence interval [CI], 17.7%-25.4%) after a first DVT and 27.9% (95% CI, 19.7%-36.1%) after a second DVT. The 5-year cumulative incidence of fatal pulmonary embolism was 2.6% (95% CI, 1.1%-4.1%) after a first DVT. Proximal DVT (relative risk [RR], 2.40; 95% CI, 1.48-3.88; P<.001), cancer (RR, 1.97; 95% CI, 1.20-3.23; P<.001), and history of a venous thromboembolism (RR, 1.71; 95% CI, 1.16-2.52; P<.01) predicted an independently increased risk of recurrent events in multivariate survival analysis. Postoperative DVT (RR, 0.27; 95% CI, 0.13-0.55; P<.001) and a long duration of oral anticoagulation therapy (RR, 0.95; 95% CI, 0.92-0.98; P<.01) involved a smaller risk of recurrent events. Sex, age, initial antithrombotic therapy, or immobilization did not affect the risk of a recurrent event. CONCLUSIONS: The recurrence rate after a symptomatic DVT is high. Patients with proximal DVT, diagnosed cancer, short duration of oral anticoagulation therapy, or a history of thromboembolic events had a higher risk of recurrent events, while patients with postoperative DVT had a lower recurrence rate. This knowledge could help identify patients who might benefit most from prolonged prophylactic treatment in various risk situations.

Adolescent↗
PubMed2003

BRCA1/2 mutation status influences somatic genetic progression in inherited and sporadic epithelial ovarian cancer cases.

Metaphase comparative genomic hybridization was used to analyze the spectrum of genetic alterations in 141 epithelial ovarian cancers from BRCA1 and BRCA2 mutation carriers, individuals with familial non-BRCA1/2 epithelial ovarian cancer, and women with nonfamilial epithelial ovarian cancer. Multiple genetic alterations were identified in almost all tumors. The high frequency with which some alterations were identified suggests the location of genes that are commonly altered during ovarian tumor development. In multiple chromosome regions, there were significant differences in alteration frequency between the four tumor types suggesting that BRCA1/2 mutation status and a family history of ovarian cancer influences the somatic genetic pathway of ovarian cancer progression. These findings were supported by hierarchical cluster analysis, which identified genetic events that tend to occur together during tumorigenesis and several alterations that were specific to tumors of a particular type. In addition, some genetic alterations were strongly associated with differences in tumor differentiation and disease stage. Taken together, these data provide molecular genetic evidence to support previous findings from histopathological studies, which suggest that clinical features of ovarian and breast tumors differ with respect to BRCA1/2 mutation status and/or cancer family history.

Chromosome Aberrations↗
PubMed1986

Relations between erythrocyte lithium efflux, blood pressure and family histories of hypertension and cardiovascular disease: studies in a factory workforce and hypertension clinic.

Sodium-dependent lithium efflux was measured in erythrocytes from 399 factory workers and 125 patients attending a hypertension clinic. Thirty-two factory workers had unsuspected essential hypertension (diastolic blood pressure phase V greater than 90 mmHg). These subjects had the same average erythrocyte lithium efflux as those with normal blood pressure, whereas lithium efflux was increased on average in the clinic hypertensives. Lithium efflux was greater in those subjects from both groups who had a family history of high blood pressure. Our clinic hypertensives did not have raised lithium efflux when they were matched for family history; the increased lithium efflux in the group as a whole (and in analysis of published reports) was explained by an excess of subjects with a family history of hypertension. Furthermore, when a family history of hypertension was present, lithium efflux was increased on average only in those whose relatives also had a cardiovascular event associated with their high blood pressure. These results, in conjunction with detailed analysis of the distributions of lithium efflux within the groups, suggest that, though not linked to blood pressure itself, an increase in lithium efflux is an inherited marker for those at risk from the cardiovascular complications associated with high blood pressure.

Adolescent↗
PubMed2002

P300 subcomponents and clinical symptoms in schizophrenia.

A small P300 component of the auditory event-related potential has been found to predict poor clinical outcome with a higher amount of thought disorders in schizophrenia and has been proposed as a marker for an underlying neurodevelopmental disorder with prominent thought disorders, early age of onset, prominent negative symptoms and positive family history. The present study was designed to confirm our previous findings with subcomponent analysis. Using dipole source analysis a temporo-basal (TB) P300 as well as a temporo-superior (TS) P300 and LP potential were separated. Fifty patients with schizophrenia (DSM-IV) were included in the study. Late auditory event-related P300 potentials were recorded to infrequent auditory stimuli after treatment psychopathology and family history were assessed. The TB-P300 amplitudes were significantly negatively correlated with thought disorders remaining after treatment and were positively correlated with age of onset. Illness duration was significantly correlated to TB-P300 and TS-P300 amplitudes in the group of patients with late onset. No significant correlations were found with negative symptoms. Family history did not show significant effects on P300. A smaller P300 in patients with more thought disorder remaining after stabilization on medication and an earlier age of onset support the hypothesis that P300 characterizes schizophrenic patients with an underlying neurodevelopmental disorder with specific clinical symptom clusters. On the other hand, diminished P300 with illness duration in the group of patients with later age of onset supports an underlying neurodegenerative progressive process in this subgroup of patients.

Adolescent↗
PubMed1994

Life events and the research diagnostic criteria endogenous subtype. A confirmation of the distinction using the Bedford College methods.

BACKGROUND: Despite the advances in biological and psychosocial assessment methods, reliable distinction between depressed patients with endogenous presentations or melancholic symptom features and those with nonendogenous presentations has remained elusive. METHODS: Ninety patients with histories of frequent unipolar episodes classified as endogenous or nonendogenous by the Research Diagnostic Criteria were interviewed with the Bedford College Life Events and Difficulties Schedule regarding the 6 months before onset of their most recent episode of depression. RESULTS: Patients meeting the Research Diagnostic Criteria for definite endogenous subtype differed significantly from patients with nonendogenous features in terms of the proportion experiencing severe life stress in the 6 months before onset of their depressive episode (P < = .04). Furthermore, survival analysis revealed a closer temporal association between severe event and depression onset among patients with nonendogenous features (P < .02). CONCLUSION: Even among patients with a history of multiple recurrences of depression, psychological stress plays an important role in the timing of onset of episodes characterized by nonendogenous features.

Adaptation, Psychological↗
PubMed1990

Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group.

BACKGROUND: Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery. It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment. Patients undergoing noncardiac surgery sometimes have postoperative cardiac events. It would be helpful to know which patients are at highest risk. METHODS: We prospectively studied 474 men with coronary artery disease (243) or at high risk for it (231) who were undergoing elective noncardiac surgery. We gathered historical, clinical, laboratory, and physiologic data during hospitalization and for 6 to 24 months after surgery. Myocardial ischemia was assessed by continuous electrocardiographic monitoring, beginning two days before surgery and continuing for two days after. RESULTS: Eighty-three patients (18 percent) had postoperative cardiac events in the hospital that were classified as ischemic events (cardiac death, myocardial infarction, or unstable angina) (15 patients), congestive heart failure (30), or ventricular tachycardia (38). Postoperative myocardial ischemia occurred in 41 percent of the monitored patients and was associated with a 2.8-fold increase in the odds of all adverse cardiac outcomes (95 percent confidence interval, 1.6 to 4.9; P less than 0.0002) and a 9.2-fold increase in the odds of an ischemic event (95 percent confidence interval, 2.0 to 42.0; P less than 0.004). Multivariate analysis showed no other clinical, historical, or perioperative variable to be independently associated with ischemic events, including cardiac-risk index, a history of previous myocardial infarction or congestive heart failure, or the occurrence of ischemia before or during surgery. CONCLUSIONS: In high-risk patients undergoing noncardiac surgery, early postoperative myocardial ischemia is an important correlate of adverse cardiac outcomes.

Adult↗
PubMed2003

Left atrioventricular plane displacement predicts cardiac mortality in patients with chronic atrial fibrillation.

AIM: The aim of the present study was to investigate if left atrioventricular plane displacement (AVPD) has a prognostic value in patients with atrial fibrillation. METHODS AND RESULTS: Left AVPD was assessed by two-dimensionally guided M-mode echocardiography in the four- and two-chamber views in 160 consecutive patients with chronic atrial fibrillation, who were followed up with regard to mortality for an average of 45 months. All-cause mortality during follow-up was 49% (n=78). AVPD was lower in patients who died compared to those who survived: 6.6+/-1.7 versus 7.5+/-1.7 mm, P=0.0005. In 49 patients (31%), death was due to chronic heart failure or acute myocardial infarction. Among those who died of cardiac events, AVPD was 6.3+/-1.6 mm, versus 7.1+/-1.8 mm among those who died of other causes, P=0.0001. In multiple logistic regression analysis, AVPD (P=0.005), age (P=0.0005), and a history of chronic heart failure (P=0.004) correlated independently with mortality. CONCLUSION: Left AVPD was clearly decreased in patients with atrial fibrillation. The decrease was most pronounced in patients who died of cardiac events, whereas it did not differ significantly between those who died of non-cardiac causes and those who survived. The discriminative value of left AVPD was limited.

Aged↗
PubMed1992

Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy.

BACKGROUND: Patients who have insulin-dependent diabetes mellitus and nephropathy have an excess of cardiovascular disease. Familial factors may in part account for this phenomenon. METHODS: We identified 61 white patients under 65 years of age with insulin-dependent diabetes who had nephropathy, and then matched them with 61 diabetic patients without nephropathy. We determined the prevalence of cardiovascular disease in the parents of these patients with use of information obtained from death certificates or from the World Health Organization questionnaire for cardiovascular disease. RESULTS: The rates of ascertainment of information were 96 percent (n = 117) for the parents of diabetic patients with nephropathy and 95 percent (n = 116) for the parents of patients without nephropathy. Cardiovascular disease was more often a direct cause of death among the parents of diabetic patients with nephropathy (40 percent vs. 22 percent, P less than 0.03), and the combined morbidity and mortality from cardiovascular disease in this group was greater than that in the parents of diabetic patients without nephropathy (31 percent vs. 14 percent, P less than 0.01). The age-adjusted and sex-adjusted relative risk of cardiovascular disease in this group of parents was 2.9 (95 percent confidence interval, 1.5 to 5.5; P less than 0.001). Moreover, a paternal history of cardiovascular disease was associated with a significantly increased risk of nephropathy in the diabetic patient after the analysis was adjusted for age, sex, and duration of diabetes (odds ratio, 3.2; 95 percent confidence interval, 1.3 to 7.9; P less than 0.01). Among the diabetic patients with nephropathy, those who had had a cardiovascular event were much more likely to have a family history of cardiovascular disease (odds ratio, 6.2; 95 percent confidence interval, 2.0 to 19.0; P less than 0.005) than those who had not had such an event. CONCLUSIONS: Among patients with insulin-dependent diabetes, a parental history of cardiovascular disease is significantly associated with the development of nephropathy and, among those with nephropathy, increases the likelihood of cardiovascular disease.

Adolescent↗
PubMed2006

Methylation and gene silencing of the Ras-related GTPase gene in lung and breast cancers.

BACKGROUND: RRAD, a small Ras-related GTPase, is highly expressed in human skeletal muscle, lung, and heart. Although loss of expression of RRAD in breast cancer cells has been reported and it may act as an oncogene, the mechanism of silencing is unknown. METHODS: We examined (1) mRNA expression of RRAD in lung and breast cancer cell lines using RT-PCR and (2) methylation status of lung and breast cancers. RESULTS: Loss of RRAD expression was found in 14 of 20 (70%) NSCLC cell lines, 11 of 11 (100%) SCLC cell lines, and 8 of 10 (80%) breast cancer cell lines; expression was not affected in normal bronchial and mammary epithelial cells. Treatment of 23 expression-negative cell lines with a demethylating agent restored expression in all cases. We developed a methylation-specific assay from the analysis of bisulfite sequencing of the 5' region of RRAD in expression-negative and positive cell lines, which resulted in good concordance between methylation and expression. Primary lung and breast cancers showed hypermethylation in 89 of 214 (42%) and 39 of 63 (62%) cases, respectively. RRAD hypermethylation correlated with smoking history and poorer prognosis in lung adenocarcinomas. CONCLUSIONS: We conclude that epigenetic silencing of RRAD is a frequent event in lung and breast cancers, and analysis of it may provide novel opportunities for prognosis and therapy of these cancers.

Adenocarcinoma↗
PubMed2004

The safety of anakinra in high-risk patients with active rheumatoid arthritis: six-month observations of patients with comorbid conditions.

OBJECTIVE: To determine in a placebo-controlled, double-blind trial the safety profile of daily anakinra (Kineret) use in patients with active rheumatoid arthritis (RA) and concurrent comorbid conditions. METHODS: In 169 centers in 9 countries, 1,414 patients with active RA were randomly assigned to receive either anakinra (100 mg) or placebo treatment (4:1 anakinra-to-placebo allocation ratio), with study drug administered by daily subcutaneous injection for 6 months. The current post hoc analysis assessed baseline comorbid conditions, and patients were considered at high risk for the occurrence of adverse events if they had a history of at least one of the following: cardiovascular event, pulmonary event, central nervous system-related event, infection, diabetes, malignancy, or renal impairment. Within each treatment group (anakinra or placebo), incidence rates were summarized for serious adverse events, infectious events, and serious infectious events in high-risk patients and compared with these incidence rates in patients without comorbid conditions. RESULTS: The majority of patients in the trial had one or more comorbid conditions. In these high-risk patients, there were no differences in the incidence of serious adverse events or infectious events between treatment groups. The incidence of serious infectious events with anakinra use was similar between high-risk patients (2.5%) and the entire study population (2.1%) and was not attributable to any single comorbidity. CONCLUSION: Results of the analysis of adverse events in patients with active RA and coexisting comorbidities suggest that the favorable safety profile of anakinra is maintained in a high-risk patient population.

Adult↗