Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up.

BACKGROUND: The role of risk stratification in normotensive patients with acute pulmonary embolism (PE) is still unclear. OBJECTIVES: We evaluated, in these patients, the usefulness of six prognostic markers for predicting in-hospital adverse events related to PE and 3-month mortality. PATIENTS/METHODS: Two hundred and one consecutive patients with confirmed acute PE and normal blood pressure, who were administered conventional anticoagulation, were recruited in a multicentre prospective cohort study with 3 months of follow-up. At baseline, they received a comprehensive risk-evaluation including echocardiographic assessment of right ventricular dysfunction, determination of troponin I, brain natriuretic peptide and D-dimer, arterial blood gas analysis and a clinical score. Primary outcome of the study was PE-related in-hospital death or clinical deterioration. Secondary outcomes were in-hospital and 3-month all-cause mortality. RESULTS: The primary outcome occurred in one patient (0.5%), who died from PE during hospitalization. The in-hospital and 3-month all-cause mortality were 2% and 9%, respectively. None of the prognostic markers was predictive of the primary outcome. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality (P = 0.02, 0.01 and < 0.01, respectively). Clinical score (HR, 4.7; 95% CI, 1.9-12.0), D-dimer (4.8; 1.4-16.3), hypoxemia (5.7; 2.1-15.1) and troponin I (7.5; 2.5-22.7) were predictors of 3-month all-cause mortality on univariate analysis. On multivariate analysis clinical score and troponin I remained independently predictive. CONCLUSIONS: We did not find prognostic markers useful as predictors of in-hospital PE-related adverse events. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality. Clinical score and troponin I independently predicted 3-month all-cause mortality.

Home-based study of anti-HIV drug regimen adherence among HIV-infected women: feasibility and preliminary results.

Collection of antiretroviral medication adherence data in the homes of HIV-infected people may have methodological advantages that can improve data quality. However, the feasibility of this approach has not been established. In addition, data on adherence, and its predictors, among HIV-infected women have been limited. Sixty-three HIV-positive women who were prescribed at least one antiretroviral drug in the last month were interviewed in their homes. A standard instrument was used to collect data on all antiretroviral medications prescribed and taken in the three days prior to the interview. Data were also collected on factors thought potentially to affect the ability to be adherent. The results of this study suggest that it is feasible to conduct home-based adherence research. Sixty-seven per cent reported taking all prescribed antiretroviral medication doses. One-third took a sub-optimal dose putting themselves at increased risk of treatment failure and the selection of resistant HIV strains. Unintentional reasons for missing doses were most commonly reported. An ability to describe the intended effect of antiretroviral therapy on HIV viral load was the best predictor of adherence. This finding is consistent with other research suggesting that adherence is associated with an understanding and belief in the effectiveness of antiretroviral therapy.

Adjustment to chronic illness among HIV-infected women.

PURPOSE: To identify factors that influence adjustment to chronic illness among HIV-infected women, using the cognitive appraisal model of stress and coping. DESIGN: Cross-sectional descriptive survey of 101 HIV-infected women living in the Northeastern United States, from December 1996 to December 1997. METHODS: During face-to-face interviews, the Meaning of Illness Questionnaire, Duke UNC Functional Social Support Questionnaire, HIV Symptom Experience Inventory and Medical Outcomes Study (MOS) Short Form Survey were used to measure appraisal of illness, social support, HIV symptom severity and adjustment to chronic illness. Hierarchical linear regression, path analysis, and procedures to test for mediation were performed. FINDINGS: The model variables explained 70% of the variance in adjustment to chronic illness. Symptom experience accounted for the greatest percentage of variance in adjustment (28%). Two of the three predicted relationships were supported as hypothesized: adjustment to chronic illness was directly influenced by appraisal of illness and by HIV-symptom experience. Social support was not found to have a direct effect on adjustment. Instead, appraisal of illness mediated the effect of social support on adjustment and symptom experience. HIV illness stage was not a significant predictor of adjustment. CONCLUSIONS: The cognitive appraisal model of stress and coping was useful for building knowledge on adjustment to chronic illness among HIV infected women. Interventions aimed at reframing negative appraisals have the potential to affect adjustment.

Women with HIV infection: the three waves of scientific inquiry.

Initial efforts to curtail the spread of HIV infection to women failed. Consequently, women are the fastest growing population newly infected with HIV. This article presents a historical look at the waves of scientific inquiry that directed research on HIV infection among women. The author proposes three distinct waves. Each has been shaped by movement within the scientific community away from traditional biomedical and public health approaches toward feminist strategies that embrace the social, political, and cultural forces that influence women's health. These waves provide both valuable insights for nurses new to the field of HIV and a framework to guide future research on women with HIV infection.

[The usefulness of the association of clinical probability, rapid plasma measurement of D-dimer, compression echography of the lower limbs and echocardiography in the diagnosis of acute pulmonary embolism]. / Utilità dell'associazione di probabilità clinica, dosaggio rapido plasmatico del D-dimero, ecografia compressiva degli arti inferiori ed ecocardiografia nella diagnosi di embolia polmonare acuta.

BACKGROUND: The aim of this study was to investigate the diagnostic utility of clinical probability, rapid plasma D-dimer assay, compression ultrasonography (CUS) and transthoracic echocardiography (TTE) in patients with suspected pulmonary embolism. METHODS: One hundred forty consecutive outpatients with suspected pulmonary embolism were enrolled in a prospective trial. We evaluated sensitivity, specificity, positive and negative predictive value of a combination of clinical probability, D-dimer, CUS and TTE using perfusion lung scan and pulmonary angiography as a combined gold standard for determining the presence or absence of pulmonary embolism. Clinical probability was assessed in accordance with the PIOPED criteria. The D-dimer (Nycocard) level was considered as abnormal > 0.3 mg/l, the CUS if incompressibility of the leg veins was showed, and the TTE if right ventricular dilation was present, in the absence of chronic pulmonary disease. The combination of these tests was considered consistent with the presence of pulmonary embolism if D-dimer plus CUS and/or TTE showed abnormal results. A pulmonary embolism was excluded if D-dimer and CUS showed normal findings or a low clinical probability was associated with normal findings of CUS and TTE. RESULTS: One hundred eleven patients were evaluated. Pulmonary embolism was present in 45/111 (40%) patients. The combination of tests showed positive findings in 39/39 patients with pulmonary embolism, negative findings in 47/50 without pulmonary embolism and non-diagnostic results in 22/111 (20%) patients (95% confidence interval--CI 12-28%). There were three false positive and no false negative results. Sensitivity and specificity were 100 and 94% respectively (95% CI 92-100% and 87-100%); positive and negative predictive values were 93 and 100% (95% CI 85-100% and 93-100%). None of these tests, separately, showed enough sensitivity and specificity. CONCLUSIONS: The combination of clinical probability, D-dimer, CUS and TTE was highly accurate to confirm or rule out pulmonary embolism.

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

The use of epidural steroid injection and manipulation on patients with chronic low back pain.

OBJECTIVES: To document the efficacy of combined epidural steroid injection (ESI) and manipulation to the lumbar spine in patients suffering from chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: The use of ESI in conjunction with lumbar manipulation has seldom been reported in the literature but has offered promising results when studied. STUDY DESIGN: Retrospective repeated-measures analysis of patients with chronic LBP who received ESIs combined with spinal manipulation. METHODS: A retrospective analysis using a repeated-measures format was performed on 17 cases of patients who had received ESI and manipulation to the lumbar spine. All patients were medically stable for chronic mechanical LBP and had experienced a suboptimal response to conventional care. The principle investigator was blinded from data outcomes when determining patient eligibility for the study. A subjective patient improvement scale was used to monitor degree of success. RESULTS: Ten of the 17 patients were eligible for the study. Patients were eliminated for lack of consistency of data collection, having received an additional procedure after conventional care, involvement of the cervical spine; one patient experienced an unrelated medical problem. After 1 yr of conventional care, the patients reported a 25.5% improvement. (Conventional care included ESI and manipulation done at separate times.) After on ESI with subsequent manipulation, these same patients reported a 50.5% improvement. Mean improvement was 25.00% (SD = 19.51, SEM 6.19, t = 4.04 and p = .0015). CONCLUSION: The use of ESI performed with manipulation seems to offer promise for a carefully selected group of patients. ESI combined with manipulation should be considered in patients who do not respond to conventional forms of care.

Epigenesis of the nurse practitioner role revisited.

In the mid-1970s, an article discussed the identity crises of nurse practitioner (NP) students which occurred during their educational experience. This article noted that NP students progress from dependence to interdependence and demonstrate regression, anxiety and conflict. Twenty years later we have also observed these changes in our own graduate students. This article describes our observations, analyzes them with respect to well-known developmental theory, and offers suggestions for teaching methodologies which enhance successful transitions through the crises.

Pharmacokinetics of nevirapine: initial single-rising-dose study in humans.

Nevirapine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, was administered for the first time to humans in a pilot study designed to investigate the pharmacokinetics and tolerance of the drug following single-dose administration to 21 HIV-1-infected individuals. The study followed a parallel design. Different groups of three subjects each were given one of seven dose levels (2.5 to 400 mg) in sequential order, starting with the lowest dose. Each subject received only one dose. Nevirapine was rapidly absorbed at all doses from a tablet formulation. Peak concentrations in plasma were generally achieved within 90 min of dose administration. Secondary peaks were also noted between 3 and 12 h or between 24 and 28 h, the latter being noted mainly in subjects receiving the higher doses. After 24 h, concentrations in plasma declined in a log-linear fashion. The terminal half-life and mean residence time exceeded 24 h in all but one subject, indicating a prolonged disposition time in this population. Both peak concentrations in plasma and areas under the plasma concentration-time curves increased proportionally with increasing dose from 2.5 to 200 mg; however, the increase in the peak concentration in plasma and the area under the plasma concentration-time curve appeared to be less than proportional at the 400-mg dose level in this small number of subjects. This observation may be due to increased clearance or decreased absorption at the highest dose or population differences in absorption or clearance between doses. Studies with a cross-over design are planned to resolve these issues. The pharmacokinetic characteristics of nevirapine are appropriate for once-daily administration. A daily 12.5-mg dose is predicted to achieve trough concentrations in plasma in the range required to totally inhibit replication of wild-type HIV-1 in human T-cell culture.

The avian retrovirus env gene family: molecular analysis of host range and antigenic variants.

The nucleotide sequence of the env gp85-coding domain from two avian sarcoma and leukosis retrovirus isolates was determined to identify host range and antigenic determinants. The predicted amino acid sequence of gp85 from a subgroup D virus isolate of the Schmidt-Ruppin strain of Rous sarcoma virus was compared with the previously reported sequences of subgroup A, B, C, and E avian sarcoma and leukosis retroviruses. Subgroup D viruses are closely related to the subgroup B viruses but have an extended host range that includes the ability to penetrate certain mammalian cells. There are 27 amino acid differences shared between the subgroup D sequence and three subgroup B sequences. At 16 of these sites, the subgroup D sequence is identical to the sequence of one or more of the other subgroup viruses (A, C, and E). The remaining 11 sites are specific to subgroup D and show some clustering in the two large variable regions that are thought to be major determinants of host range. Biological analysis of recombinant viruses containing a dominant selectable marker confirmed the role of the gp85-coding domain in determining the host range of the subgroup D virus in the infection of mammalian cells. We also compared the sequence of the gp85-coding domain from two subgroup A viruses, Rous-associated virus type 1 and a subgroup A virus of the Schmidt-Ruppin strain of Rous sarcoma virus. The comparison revealed 24 nonconservative amino acid changes, of which 6 result in changes in potential glycosylation sites. The positions of 10 amino acid differences are coincident with the positions of 10 differences found between two subgroup B virus env gene sequences. These 10 sites identify seven domains in the sequence which may constitute determinants of type-specific antigenicity. Using a molecular recombinant, we demonstrated that type-specific neutralization of two subgroup A viruses was associated with the gp85-coding domain of the virus.

The new AN69 membrane in biofiltration (BF): 18 month's follow-up.

BF is a dialytic procedure employing the new AN69 polyacrylonitrile membrane, which is more permeable to both water and solutes than the traditional AN69. A postdilutional bicarbonate infusion is necessary in BF. The treatment time is 3 hours. Six patients, previously on regular acetate (HD) or bicarbonate dialysis (BHD) with AN69 were treated for 18 months with BF. Biochemical and hematological parameters (BUN, creatinine, uric acid, CA, P, K, Na, blood pH, HCO3, hematocrit) and clinical signs were evaluated in BF, and compared to those of HD and BHD. An improvement in biochemical and hematological parameters accompanied by better clinical signs was seen in BF as compared to HD and BHD. In our opinion this is due both to better removal of small and middle molecules and the bicarbonate infusion, and to the shorter dialytic session.

env genes of avian retroviruses: nucleotide sequence and molecular recombinants define host range determinants.

The env gene of avian sarcoma and leukosis retroviruses is allelic in the virus population permitting the virus to use different host cell receptors. This polymorphism has allowed the classification of these viruses into different subgroups. In order to understand further the role of viral sequences involved in determining this host range phenomenon, we constructed molecular recombinants between subgroup A, B, and E viruses and showed that the host range determinant defining subgroup specificity was located within a 1.1-kb region of the genome that included most of the coding region for the env gene product gp85. We also determined the nucleotide sequence of the region of the env gene encoding gp85 for virus isolates representing subgroup A and B viruses. We compared the predicted amino acid sequences of gp85 to themselves and to the previously published sequences of subgroup B, C, and E env genes. Based on these comparisons, we draw the following conclusions: Within the gp85 coding domain, there are four variable regions (VR-1 to VR-4) ranging in size from 9 to 52 amino acids. The variable regions are located in the same relative positions for each of the env gene alleles compared. The variable regions range in homology from 42% (A compared to B) to 57% (C compared to E) in pairwise comparisons; the flanking conserved domains are on average 95% homologous. The sequences of three different subgroup B virus isolates are highly homologous in both the conserved and variable regions. Secondary structure predictions suggest that gp85 is composed mostly of beta sheet topology. Hydrophilic loops within the variable regions may define sites of receptor interaction and binding sites for subgroup specific neutralizing antibodies.

The 'request for proposal' approach to designation of a trauma center.

Although much has been written about the need for trauma centers, little has been published concerning the method of designating one. The New Mexico Emergency Medical Service Bureau of the Health and Environment Department invited all hospitals in the region. A selection committee made up of two trauma surgeons and an emergency physician reviewed the RFP documents and visited each competing hospital. The selection committee's report was presented to the New Mexico Medical Society in an open forum. The Emergency Medical Service Bureau reviewed both the report and the response of the medical society, which was supportive. Finally, a designation was made by the bureau and announced by the governor, and was well accepted by all of the participating parties.