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Biomedical subjects

B Jovanovic

Publications and source records attributed to B Jovanovic.

At least 19 recordsLinked to original sources

Perinucleolar compartment prevalence has an independent prognostic value for breast cancer.

The perinucleolar compartment (PNC) is a multicomponent nuclear structure enriched with RNAs transcribed by RNA pol III and RNA binding proteins. Studies in cultured cells showed an association between PNC and transformed phenotype. To evaluate the relationship between structure and malignancy in vivo, we examined PNC prevalence (the percentage of cells containing at least one PNC) in normal and cancerous paraffin-embedded breast tissues using immunohistochemistry against a PNC-associated protein. Five hundred nuclei in the most active area of each sample were scored for PNC prevalence. The results show that PNC prevalence significantly correlates with the progression of breast cancer (by the criteria of staging). PNC prevalence in primary tumors, lymph nodes, and distant metastases shows a stepwise increase from a median of 23% in primary tumors to approximately 100% in distant metastases. In addition, univariate and multivariate (controlling for tumor size and grade) analyses show that early-stage patients with invasive ductal carcinomas containing a higher PNC prevalence have a significantly poorer prognosis. These findings link PNC prevalence with the progression of breast cancer in vivo and suggest that PNC-containing cells have metastatic advantages. These findings also show the potential of PNC prevalence as a prognostic marker for breast cancer.

Aged↗

The training curriculum in hospital infection control.

Standardised training curricula for infection control nurses (ICNs) and recognition of the specialty exist in many European countries, but infection control physician (ICP) is not a specialty recognised by the UEMS. To gather information on curricula for ICPs, members of the ESCMID Study Group on Nosocomial Infections received a questionnaire. There is discussion about which 'professions' should be included in an infection control team. Within the 12 countries included, the average full-time equivalents (FTEs) for ICPs and ICNs per 1000 beds were 1.2 and 3.4, respectively. In addition to ICNs and ICPs, an infection control team should also include a data manager, an epidemiologist, secretarial/administrative support, and possibly, surveillance technicians. Overall, the composition of an ideal infection control team was estimated to be 9.3 FTE per 1000 beds. The background of ICPs can be clinical microbiology or infectious diseases. Among the participants, it was predominantly clinical microbiology. The ideal training curriculum for the ICP should include 6 years of postgraduate training. Of these, at least 2 years should be 'clinical training' (e.g., internal medicine) to acquire experience in the management of high-risk patients. Furthermore, training with regard to infection control and hospital epidemiology should be offered as a 'common trunk' for those being trained in clinical microbiology or infectious diseases. Important issues that remain are: implementation/standardisation of training curricula for doctors, recognition of ICP as a separate specialty or sub-specialty of clinical microbiology and/or infectious diseases, validation of on-the-job training facilities in terms of the number of doctors and nurses who can give training and the category of patients/problems present, and mandatory postgraduate education/continuing medical education specific for infection control for doctors and nurses in the field.

Cross Infection↗

Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report.

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.

Biomarkers, Tumor↗

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission.

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.

Acute Disease↗

Impaired egress rather than increased access: an important independent predictor of erosive oesophagitis.

Oesophagitis severity is related to total oesophageal acid exposure, which is in turn dependent upon both the number reflux events and the rate of refluxate clearance. This study examined differences in the frequency of reflux events and the characteristics of oesophageal acid exposure in asymptomatic controls and gastro-oesophageal reflux disease (GORD) patients both with and without oesophagitis. Nine controls and 38 patients with GORD were studied. All patients underwent upper endoscopy, videofluoroscopy, determination of resting lower oesophageal sphincter pressure (LOSP) and 24 h pH monitoring. Analysis was performed with subjects grouped as controls, non-erosive GORD and oesophagitis. A second analysis was performed with subjects grouped by hiatal hernia size. Statistical comparisons were made using anovaand unpairedt-tests. Patients with oesophagitis had significantly larger hiatal hernias, greater oesophageal acid exposure, more prolonged episodes of reflux and longer acid clearance times than did controls and patients with non-erosive GORD. No significant difference was seen in the number of reflux events. Increasing hiatal hernia size was significantly associated with increasing oesophageal acid exposure, number of prolonged reflux events and prolonged acid clearance times. Oesophagitis patients have significantly greater oesophageal acid exposure than subjects with non-erosive GORD. Increased oesophageal acid exposure in oesophagitis is attributable to impaired acid clearance and the greatest impairments in refluxate clearance occur in patients with large hiatal hernias.

Adult↗

Long-term outcome of a prospective trial of steroid withdrawal after kidney transplantation.

BACKGROUND: Steroid withdrawal (SW) after kidney transplantation is desirable to avoid associated serious side effects. We studied the long-term outcome of a group of kidney transplant recipients who underwent SW. METHODS: Between 1991 and 1993, kidney transplant recipients (N = 12) who had posttransplantation diabetes were entered in a prospective trial of SW. These patients were compared with a demographically similar comparison cohort (N = 66). End points of the study were patient and graft survival, incidence of late acute and chronic rejection, and changes in diabetes management. RESULTS: Previously published data from the SW group at 15 months of follow-up indicated improvement in diabetes control without any adverse effect on patient or graft actuarial survival. At long-term follow-up (mean, 56 months) the improvement in diabetes management was not detectable. The incidence of late acute rejection in SW and cohort groups was 42% and 8%, respectively (P = .006). Likewise, the incidence of chronic rejection in the SW versus cohort group was 42% and 12%, respectively (P = .014). CONCLUSIONS: Although SW appeared to be successful initially, our long-term data indicate that SW significantly increases the risk of late acute rejection and chronic rejection episodes without benefits in posttransplantation diabetes management. Steroid withdrawal in patients with posttransplantation diabetes should be approached with caution.

Acute Disease↗

On planning the number of controls in cross-sectional studies using previous studies: an application in occupational epidemiology.

BACKGROUND: In occupational epidemiology, it is common to use cross-sectional studies comparing exposed with matched non-exposed populations. When several such past studies are available within a relatively short time frame, it may be possible to use their control groups to reduce the number of controls in a new study and thus reduce its cost. METHODS: We compare existing non-exposed populations within a standard random-effects model, to explore the natural between population variability and to compute the power increase when including these populations. An example is given from respiratory epidemiology, with the forced expiratory volume in 1 s as the outcome, using 13 previously-collected control populations obtained in recent studies. RESULTS: We show that the reduction in the number of controls needed for a new study is equal to the ratio of the between subjects and the between group variance, observed in controls in previous studies. In the present example, the reduction in the number of controls needed for a new study was found to be 18. An optimal allocation of resources is obtained in this framework. CONCLUSIONS: The use of past available control groups provides a significant reduction in cost only if they are very homogeneous, compared to the between-subject variance.

Analysis of Variance↗

Prediction of relapse within eight weeks after an acute asthma exacerbation in adults.

Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management.

Acute Disease↗

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

BACKGROUND: Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. OBJECTIVE: To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. METHODS: A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. MAIN OUTCOME MEASURES: Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. RESULTS: The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). CONCLUSIONS: Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.

Acute Disease↗

An evaluation of a chest pain diagnostic protocol to exclude acute cardiac ischemia in the emergency department.

BACKGROUND: Although accelerated diagnostic protocols are being increasingly used in emergency departments to diagnose acute cardiac ischemia, there have been no prospective evaluations of a chest pain diagnostic protocol with serial determinations of creatine kinase MB isoenzyme and mandatory exercise electrocardiography (ExECG). METHODS: Prospective cross-sectional study in which chest pain protocol results were compared with final (reference) diagnoses of acute cardiac ischemia (including acute myocardial infarction and unstable angina). Patients in need of hospital admission but at low probability (by a validated algorithm) for acute myocardial infarction were examined for exclusions: known coronary artery disease, cardiac complications, severe comorbidities, or inability to perform exercise testing. A 12-hour diagnostic protocol included serial measurements of creatine kinase MB, ECG, and clinical assessments followed by ExECG for those with negative initial serial testing. Reference diagnoses were established during hospitalization and diagnostic accuracy was assessed. RESULTS: The study group of 317 patients was 54% male and 65% black, and had a mean age of 46.6 years; 9.5% had a final diagnosis of acute cardiac ischemia. For this diagnosis, the protocol had a sensitivity of 90.0% (95% confidence interval, 72.3%-97.4%); specificity, 50.5% (95% confidence interval, 44.6%-56.4%); positive predictive value, 16.0%; and negative predictive value, 98.0%. Creatine kinase MB, serial ECGs, and ExECG each made a contribution to improved sensitivity and accuracy, whereas clinical reassessments were less discriminating, as indicated by protocol's receiver operating characteristic curve. CONCLUSIONS: A chest pain diagnostic protocol achieved high sensitivity and improved specificity over the standard emergency department workup. There were no adverse advents associated with early ExECG.

Algorithms↗

Feasibility of a rapid diagnostic protocol for an emergency department chest pain unit.

STUDY OBJECTIVE: To evaluate the applicability of a short-stay protocol for exclusion of acute ischemic heart disease without hospital admission and to analyze these results in the context of a conceptual model. METHODS: An observational study of patients who presented with chest pain to the emergency department of an 886-bed inner-city municipal hospital and who needed hospital admission to rule out acute myocardial infarction (AMI). Patients were assessed by ED attending physicians to determine eligibility for an alternative, 12-hour protocol in an ED chest pain observation unit (CPOU) followed by immediate exercise testing. Outcome measures were proportion of patients eligible for the short-stay protocol, risk factor profile, and reasons for exclusion. RESULTS: Of 500 patients screened, 446 had sufficient data points to determine protocol eligibility. Of these, 238 (53.3%; 95% confidence interval [CI], 48.7% to 57.9%) were found to have low probability for AMI. After study exclusion criteria were applied to the patient cohort, 63 patients (14.1%; 95% CI, 10.9% to 17.3%) were eligible for the protocol. The most common reasons for exclusion were history of coronary artery disease (46%) and inability to perform an interpretable exercise tolerance test (42%). CONCLUSION: Although most admitted patients with chest pain (53%) were at low probability for AMI, only a minority (14%) were eligible for a short-stay protocol that required patients to be free of known coronary artery disease and able to perform an exercise tolerance test. Factors affecting the operations and efficiency of a CPOU include clinical characteristics of the target patient population, protocol tests used, and hospital occupancy and reimbursement patterns.

Acute Disease↗

Risk behavior and HIV seroincidence among out-of-treatment injection drug users: a four-year prospective study.

We monitored trends in HIV risk behaviors and seroconversion among out-of-treatment injection drug users (IDUs) receiving street-based outreach intervention. Beginning in 1988, 641 HIV-seronegative IDUs were recruited by targeted sampling methods to reflect broader IDU populations and were followed for 4 years (1988-1992). All were active injectors not in treatment when recruited. Cohort members were targets of HIV-prevention outreach. The intervention was guided by the Indigenous Leader Outreach Model: Exaddicts deliver HIV-prevention services targeting IDU social networks in community settings. Primary outcome measures were HIV seroconversion and HIV risk behaviors. Observed incidence of HIV infection decreased, from 8.4 to 2.4 per 100 person-years. Prevalence of drug risk behaviors also decreased, from 100 to 14%. Seroconversion was associated with injection risk behavior [risk ratio (RR) = 9.8]. Sex risk behavior also decreased, but less dramatically, from 71 to 45%. Out-of-treatment IDUs in Chicago have reduced their rates of new HIV infection by reducing their injection risk behavior. New infections were strongly associated with injection risk behavior but not with sex risk behavior.

Adolescent↗

Nosocomial infections in a burn intensive care unit.

Although many studies have reviewed burn wound infections (BWIs) in burn patients, few have prospectively surveyed other nosocomial infections. Seriously burned patients are clearly at increased risk for infection due to the nature of the burn injury itself, immunocompromising effects of burn injury, prolonged hospital stays, and invasive diagnostic and therapeutic procedures. Over 6 months, we prospectively reviewed all patients admitted to our burn intensive care unit (BICU) for nosocomial infections. We used standard CDC definitions of nosocomial infections (NIs). Because we had previously documented a high incidence of nosocomial pneumonias in these patients, we were particularly interested in determining risk factors for nosocomial pneumonia. The total census during the study period was 57. There were 40 discharges and deaths. Surveillance demonstrated 36 nosocomial infections in 26 patients, for a total of 90 nosocomial infections per 100 discharges and deaths, or 32.3 NIs/1000 patient days. Infections included 22 pneumonias, 10 urinary tract infections, two bacteraemias, one BWI and one episode of cellulitis. Intubation was strongly associated with nosocomial infection, particularly with pneumonia, BWI and bacteraemia. Sixty per cent of all patients were intubated at some time during their BICU stay, but 88 per cent of those who developed a nosocomial infection were intubated (P < 0.001). Inhalation injury was less significant than intubation in the development of nosocomial infection. All patients who developed pneumonia or a BWI were intubated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Handwashing machines, handwashing compliance, and potential for cross-contamination.

Although handwashing is considered an important factor in the prevention of nosocomial infections, the optimal technique has not been determined and compliance is often difficult to obtain. Handwashing compliance is particularly important in intensive care areas of the hospital. In an effort to improve HW compliance, the surgical intensive care unit in our hospital purchased three handwashing machines. Four months after installation of the handwashing machines, an outbreak of methicillin-resistant Staphylococcus aureus occurred in the intensive care unit. As part of evaluating the outbreak, we cultured the handwashing machines, including the portholes and the paper towel dispenser. Cultures were positive for methicillin-resistant Staphylococcus epidermidis, Achromobacter species, and Streptococcus viridans. The design of the handwashing machines made contamination of sleeves and already-washed hands possible. An observational study revealed that handwashing compliance was poor but improved from 22% to 38% when the handwashing machines were in use. Nurses preferred handwashing at the sink and physicians preferred the handwashing machine. Handwashing machines may increase handwashing compliance because of their novelty, but they may also result in novel problems.

Cooperative Behavior↗

Real and apparent tuberculin skin test conversions in a group of medical students.

OBJECTIVE: To evaluate tuberculin skin test (TST) conversions among a group of medical students. DESIGN: Questionnaire sent to a medical school class in whom a cluster of TST conversions was noted, and interview and repeat TST of students with conversion. SETTING: County hospital and associated medical school. SUBJECTS: Medical students, after their third year in medical school. RESULTS: Of 165 students in the class, 115 (70%) responded; 10 reported TST conversions between the beginning of the third and the fourth year. Seven of 10 were interviewed, and all 10 were retested. Five students, all in a cohort who tested each other during a clinical clerkship with a tuberculin material previously reported to be associated with a high rate of false-positive TSTs, were TST negative on repeat. Five had persistently positive TSTs. One was exposed during a psychiatry clerkship to a resident with pulmonary tuberculosis. Four students appeared to have converted their TST during their third year in medical school. All four did their medicine clerkship at a large county hospital (P < 0.02; odds ratio = 16.4) that had few infection control measures in place for tuberculosis isolation during the time of their exposure. CONCLUSIONS: We recommend that medical students, as well as other healthcare professions students, be educated about infection control practices and skin tested at least annually during clinical training years.

Chicago↗

A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.

A community-wide study was conducted in 16 short-stay hospitals in metropolitan Worcester, Mass, to examine the incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism in patients hospitalized between July 1, 1985, and December 31, 1986. The average annual incidence of deep vein thrombosis alone was 48 per 100,000, while the incidence of pulmonary embolism with or without deep vein thrombosis was 23 per 100,000. The incidence rates of deep vein thrombosis and pulmonary embolism increased exponentially with age. The in-hospital case-fatality rate of venous thromboembolism was 12%. Among patients discharged from the hospital, the long-term case-fatality rates were 19%, 25%, and 30% at 1, 2, and 3 years after hospital discharge. Extrapolation of the data from this population-based study suggests that there are approximately 170,000 new cases of clinically recognized venous thromboembolism in patients treated in short-stay hospitals in the United States each year, and 99,000 hospitalizations for recurrent disease. Because of the silent nature of this disease and the low rate of autopsy in the United States, the total incidence, prevalence, and mortality rates of venous thromboembolism remain elusive.

Adolescent↗