Interprofessional education on complex patients in nursing homes: a focus group study.

BACKGROUND: An ageing population leads up to increasing multi-morbidity and polypharmacy. This demands a comprehensive and interprofessional approach in meeting patients' complex needs. This study describes graduate students' experiences of working practice based in interprofessional teams with complex patients' care needs in nursing homes. METHOD: Students from advanced geriatric nursing, clinical nutrition, dentistry, medicine and pharmacy at the University of Oslo in Norway were assigned to groups to examine and develop a care plan for a nursing home patient during a course. Focus groups were used, 21 graduate students participating in four groups. Data were collected during spring 2018, were inductively analysed according to a thematic analysis method (Systematic Text Condensation). An analytical framework of co-ordination practices was applied to get an in-depth understanding of the data. RESULTS: Three themes were identified: 1) Complex patients as learning opportunities- an eye-opener for future interprofessional collaboration 2) A cobweb of relations, and 3) Structural facilitators for new collective knowledge. Graduate university students experienced interprofessional education (IPE) on complex patients in nursing homes as a comprehensive learning arena. Overall, different co-ordination practices for work organization among the students were identified. CONCLUSIONS: IPE in nursing homes facilitated the students' scope from a fragmented approach of the patients towards a relational and collaborative practice that can improve patient care and strengthen understanding of IPE. The study also demonstrated the need for preparatory teamwork training to gain maximum benefit from the experience. Something that can be organized by the education institutions in the form of a stepwise learning module and as an online pre-training course in interprofessional teamwork. Further, focusing on the need for well thought through processes of the activity by the institutions and the timing the practice component in students' curricula. This could ensure that IPE is experienced more efficient by the students.

Remifentanil as an adjunct to anaesthesia for electroconvulsive therapy fails to confer long-term benefits.

BACKGROUND: Adding the µ-opioid receptor agonist remifentanil to agents used to induce general anaesthesia in electroconvulsive therapy (ECT) can reduce the required doses of induction agents and their unfavourable effects on seizure threshold and quality. However, whether remifentanil has favourable long-term treatment effects in terms of response and remission rates, speed of response and remission, and side-effects has not been studied. METHODS: This retrospective, register-based cohort study involved patients with major depression consecutively treated at two units at different hospitals in Norway with the same ECT procedure. Both units used thiopental for ECT anaesthesia, but only one unit added remifentanil (R+; n=47; 541 sessions), whereas the other did not (R-; n=119; 1166 sessions). A Cox proportional hazards model for interval-censored data was conducted to examine the effects of remifentanil on the time to response and remission from depressive symptoms, whilst adjusting for age, sex, and baseline depression score. RESULTS: Both R+ and R- patients showed substantial reductions of depressive symptoms, with no difference in the response (76% in both groups) or remission (63% vs 65%) rate. However, R+ patients responded (hazard ratio=0.59; 95% confidence interval: 0.4-0.8) and remitted (hazard ratio=0.72; 95% confidence interval: 0.5-1.0) more slowly, and reported more often side-effects of nausea (30% vs 8%; P<0.001), dizziness (22% vs 8%; P=0.027), and headache (48% vs 23%; P=0.004). CONCLUSIONS: The use of adjunctive remifentanil was associated with more short-term side-effects and no favourable long-term clinical outcomes. The practice of routinely adding remifentanil to barbiturate anaesthesia should therefore be reconsidered.

Use of medicines, adherence and attitudes to medicines among persons with chronic spinal cord injury.

STUDY DESIGN: A cross-sectional study. OBJECTIVES: To describe the use of medicines and adherence among persons with spinal cord injury (SCI). Further, to examine the influence of pain, spasms and beliefs about medicines on adherence. SETTING: Sunnaas Rehabilitation Hospital, Norway. METHODS: Persons (⩾18 years) with chronic SCI (more than 1-year post injury), using at least one drug regularly, and admitted for a follow-up stay at Sunnaas Rehabilitation Hospital were included. Participants were interviewed about their drug regimen and filled out validated self-report questionnaires: Morisky Medication Adherence Scale (MMAS-8), beliefs about medicines questionnaire (BMQ), visual analogue scale (VAS) for pain and modified Penn spasm frequency scale (mPSFS). RESULTS: The 105 participants used in average 4.2 drugs regularly (range, 1-15), and 70% reported high or moderate adherence to their treatment. Of the 39 participants using oral spasmolytics, 74% reported high or moderate adherence to these drugs. A total of 97% of the participants reported high perceptions of necessity to their treatment and 54% reported a high level of concern. CONCLUSION: The persons with SCI included in this study used in average the same number of regular drugs compared to persons with other chronic conditions. Regardless of high overall adherence, the participants were more concerned about their medicines compared to other patient groups. Further studies are required for understanding adherence and attitudes toward medicines in this population, especially to help the persons with chronic SCI feel safe about their drug regimen.

Nursing staffs self-perceived outcome from a rehabilitation 24/7 educational programme - a mixed-methods study in stroke care.

BACKGROUND: During the past two decades, attempts have been made to describe nurses' contributions to the rehabilitation of inpatients following stroke. There is currently a lack of interventions that integrate the diversity of nurses' role and functions in stroke rehabilitation and explore their effect on patient outcomes. Using a systematic evidence- and theory-based design, we developed an educational programme, Rehabilitation 24/7, for nursing staff working in stroke rehabilitation aiming at two target behaviours; working systematically with a rehabilitative approach in all aspects of patient care and working deliberately and systematically with patients' goals. The aim of this study was to assess nursing staff members' self-perceived outcome related to their capability, opportunity and motivation to work with a rehabilitative approach after participating in the stroke Rehabilitation 24/7 educational programme. METHODS: A convergent mixed-method design was applied consisting of a survey and semi-structured interviews. Data collection was undertaken between February and June 2016. Data from the questionnaires (N = 33) distributed before and after the intervention were analysed using descriptive statistics and Wilcoxon sign rank test. The interviews (N = 10) were analysed using deductive content analysis. After analysing questionnaires and interviews separately, the results were merged in a side by side comparison presented in the discussion. RESULTS: The results from both the quantitative and qualitative analyses indicate that the educational programme shaped the target behaviours that we aimed to change by addressing the nursing staff's capability, opportunity and motivation and hence could strengthen the nursing staff's contribution to inpatient stroke rehabilitation. A number of behaviours changed significantly, and the qualitative results indicated that the staff experienced increased focus on their role and functions in rehabilitation practice. CONCLUSION: Our study provides an understanding of the outcome of the Rehabilitation 24/7 educational programme on nursing staff's behaviours. A mixed-methods approach provided extended knowledge of the changes in the nursing staff members' self-percived behaviours after the intervention. These changes suggest that educating the nursing staff on rehabilitation using the Rehabilitation 24/7 programme strengthened their knowledge and beliefs about rehabilitation, goal-setting as well as their role and functions.

Placental transfer and vascular effects of pharmaceutical drugs in the human placenta ex vivo: A review.

At least 80% of pregnant woman in Europe use at least one medication during their pregnancy. The majority of these drugs are prescribed off-label. A better understanding of drug transport and effects in the placenta can provide an improved pharmacological basis to rationalize drug and dose selection for prescription. Here we provide a narrative review of studies that used the ex vivo placenta perfusion model to study placental drug transport and vascular effects of pharmaceuticals. For studies on placental transfer, we found that the methodology used varied substantially between studies as well as the way in which data was reported. Across the different therapeutic groups, ex vivo measurements of transfer generally corresponded well to in vivo findings. Still, further standardization of the perfusion technique would facilitate a broader use of perfusion data, e.g. in the context of quantitative systems pharmacology models as has been explored in recent years. Only few studies investigated the effects of drugs on the vascular tone using the ex vivo dual-side perfusion model. The model was particularly applied to study vasodilatory effects of pharmaceuticals in the fetoplacental circulation. In conclusion, the ex vivo dually perfused human cotyledon provides a relevant system to gain insights in placental drug disposition and study effects on the fetoplacental vasculature.

Handling and reporting missing data in training load and injury risk research.

PURPOSE: To map the current practice of handling missing data in the field of training load and injury risk and to determine how missing data in training load should be handled. METHODS: A systematic review of the training load and injury risk literature was performed to determine how missing data are reported and handled. We ran simulations to compare the accuracy of modelling a predetermined relationship between training load and injury risk following handling missing data with different methods. The simulations were based on a Norwegian Premier League men's football dataset (n = 39). Internal training load was measured with the session Rating of Perceived Exertion (sRPE). External training load was the total distance covered measured by a global positioning systems (GPS) device. RESULTS: Only 37 (34%) of 108 studies reported whether training load had any missing observations. Multiple Imputation using Predicted Mean Matching was the best method of handling missing data across multiple scenarios. CONCLUSION: Studies of training load and injury risk should report the extent of missing data, and how they are handled. Multiple Imputation with Predicted Mean Matching should be used when imputing sRPE and GPS variables.

Patients' perceptions of medicines information received at hospital discharge in Norway: a qualitative interview study.

Background Insufficient transfer of medicines information is a common challenge at discharge from hospital. Following discharge, home dwelling patients are expected to manage their medicines themselves and adequate counselling is an important prerequisite for patient empowerment and self-efficacy for medicines management. Objective The aim was to identify patients' needs for medicines information after discharge from hospital, including the patients' perception and appraisal of the information they received at discharge. Setting The study enrolled patients discharged from three medical wards at a secondary care hospital in Oslo, Norway. Method Patients were included at the hospital, at or close to the day of discharge and qualitative, semi-structured interviews were performed during the first 2 weeks after discharge. Eligible patients were receiving medicines treatment on admission and after discharge, were handling the medicines themselves, and discharged to their own home. Data were collected in 2017. Interviews were analysed with thematic analysis inspired by Systematic Text Condensation. Main outcome measure Patients' perceptions of medicines information. Results In total, 12 patients were interviewed. They were discharged in equal numbers from the three wards, representing both sexes and a broad age range. Patients perceive medicines information as a continuum and not limited to specific encounters, like the discharge conversation. They gain information in several ways; by receiving information from health care professionals, through observations, and by seeking it themselves. Some thought they could have been better informed about adverse reactions and how to manage life while being a medicines user. Others felt they did not want or need more information. Patients employ various strategies for coping with their use of medicines, influencing their self-efficacy towards medicine management. Conclusion Medicines information should focus on empowering the patients throughout the hospital stay and not solely at discharge, taking into account the individual patient's needs for information, preferences and prior knowledge.

Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage : Kinetic profile, relationship to interleukin 6 and infarct size.

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

A preliminary report on the neuropsychologic sequelae of human immunodeficiency virus.

The neuropsychologic sequelae of acquired immunodeficiency syndrome and human immunodeficiency virus were studied by comparing the results of a neuropsychologic test battery administered to the following three groups of Danish homosexual men: 20 patients with acquired immunodeficiency syndrome, 20 asymptomatic subjects who tested positive for the human immunodeficiency virus, and a matched control group of 20 subjects who tested negative for the human immunodeficiency virus. The group with acquired immunodeficiency syndrome performed significantly worse than the control subjects on the tests measuring concentration, memory, and psychomotor speed. The group with human immunodeficiency virus performed significantly worse than the control subjects on the tests measuring verbal memory and psychomotor speed. On the other tests, their results varied. The study supports the hypothesis that not only patients with acquired immunodeficiency syndrome but also asymptomatic subjects with human immunodeficiency virus may be neuropsychologically impaired early in the course of the disease.

Suppression of p24 antigen in sera from HIV-infected individuals with low-dose alpha-interferon and zidovudine: a pilot study.

On the basis of the observations that HIV antigenaemia indicates a high risk of progression to AIDS and that zidovudine and alpha-interferon act synergistically against HIV replication in vitro, we performed a pilot trial including 12 HIV-infected asymptomatic patients with detectable p24 antigen in serum. The patients received low-dose lymphoblastoid alpha-interferon alone for 4 weeks followed by a combination of interferon and low-dose zidovudine for a further 16 weeks. The median p24 antigen level decreased significantly (P less than 0.01), the decrease being most pronounced at week 5. Decreases in haemoglobin and neutrophil counts were observed. Four patients required reduction of the zidovudine dose and three patients were transfused. In conclusion, the drug combination was capable of reducing the serum level of HIV p24 antigen and it was tolerated by the patients. Further studies are required to evaluate the clinical implications of these observations.

Development of resistance of zidovudine (ZDV) and didanosine (ddI) in HIV from patients in ZDV, ddI and alternating ZDV/ddI therapy.

OBJECTIVE: To study development of phenotypic and genotypic resistance against zidovudine (ZDV) and didanosine (ddI) during 24 months of mono- and monthly alternating therapy. PATIENTS: Forty-six patients, not previously treated with antiretroviral drugs, were included in the study. METHODS: ZDV and ddI sensitivity were determined in a biological assay based on production of HIV antigen in cultures of CD4+ lymphocytes. The ZDV-associated mutations at codon 41 and 215, and the ddI-associated mutation at codon 74 of the reverse transcriptase (RT) gene were analysed using selective polymerase chain reaction on DNA from peripheral blood mononuclear cells. The biological phenotype [syncytium-inducing (SI)/non-SI(NSI)] of the viral isolates was assessed using a MT2 assay. RESULTS: Of the patients, 82% in ZDV therapy and 73% in alternating therapy developed phenotypic resistant HIV [median inhibitory concentration (IC50) > 0.1 microM]. Patients treated for 1 year with ddI (monotherapy or alternating) had significant higher ddI IC50 values than patients in ZDV monotherapy. During ZDV and alternating therapy, 67 and 75% of the patients, respectively, developed mutations in RT codon 41, whereas 83 and 75%, respectively, developed mutations in codon 215. In patients treated with ddI, 60% developed mutations in codon 74, whereas none of the patients in either alternating ZDV/ddI or ZDV therapy developed this mutation. Forty-six per cent of the patients had SI HIV at start of therapy. Four patients switched from SI to NSI during either ZDV, ddI or alternating therapy. Faster development of resistance was associated with the SI phenotype. CONCLUSIONS: No difference in either phenotypic ZDV or ddI resistance, or genotypic ZDV resistance could be demonstrated during monotherapy or monthly alternating ZDV/ddI therapy, whereas genotypic ddI resistance (mutation in RT codon 74) only were detected in patients in ddI monotherapy. In addition, we found that development of phenotypic and genotypic resistance was faster in patients harbouring SI isolates, and that switches from SI to NSI during therapy was independent of the type of therapy.

Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins.

The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan structures may be implicated in CD4-gp120 binding.

Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial.

OBJECTIVES: To compare the efficacy and safety of indinavir 800 mg three times a day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a day and saquinavir 400 mg twice a day, when administered with two nucleoside analogues. DESIGN: A randomized, open-labelled, controlled trial. Two hundred and eighty-four patients started randomized treatment. The primary end-point was the proportion of patients with HIV RNA of 200 copies/ml or less (Roche Amplicor) and HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 months. Analysis was performed as intent-to-treat, and missing values were accounted for as failures. RESULTS: As of 1 May 1998, 269 patients should have completed 24 weeks of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07. In antiretroviral drug-naive patients (n = 119), the corresponding figures were 63, 57, and 89% (P < 0.01), whereas among drug-experienced patients (n = 165) 77, 74, and 77% had HIV RNA of 200 copies/ml or less (P = 0.90). The same pattern was observed in the ultradirect analysis. All three regimens were generally safe, but significantly more patients in the ritonavir group (37%) stopped treatment because of adverse drug reactions compared with the indinavir group (8%) and the ritonavir plus saquinavir group (16%) (P < 0.001). CONCLUSIONS: Treatment with saquinavir plus ritonavir in combination with two nucleoside analogues is generally safe, and has superior short-term antiviral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow-up is needed to determine the durability of the viral response.

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors.

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can be a target for MAb-mediated virus neutralization.

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected patients by CMV polymerase chain reaction and the antigenemia test.

OBJECTIVE: Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia tests as methods for early detection of CMV disease. METHODS: Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 x 10(6)/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year. RESULTS: Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model. CONCLUSIONS: The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.

Hydrogen bond formation as basis for radical scavenging activity: a structure-activity study of C-methylated dihydrochalcones from Myrica gale and structurally related acetophenones.

A naturally occurring flavonoid, myrigalone B (2',6' -dihydroxy-4'-methoxy-3',5'-dimethyl-dihydrochal-cone) is an effective antioxidant and scavenger of the diphenylpicrylhydrazyl radical, while the closely related angoletin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethyl-dihydrochalcone) is inactive. From NMR spectra, it appears that myrigalone B has a time-averaged conformation in which the substituted aromatic ring is orthogonal to the carbonyl group, while angoletin is coplanar. By donating a phenolic hydrogen in radical scavenging, myrigalone B will lose its symmetrical structure and may thereby change to a coplanar conformation forming a strong intramolecular hydrogen bond between the remaining phenolic hydrogen and the carbonyl group. The energy gain entailed would then appear to be a driving force for the radical scavenging by myrigalone B. Angoletin, being coplanar, lacks this driving force. To verify this hypothesis, the conformation and radical scavenging activity of a series of phenolic acetophenones were studied. All substances that had an orthogonal conformation and could form intramolecular hydrogen bonds by loss of a phenolic hydrogen were DPPH scavengers, while compounds lacking these properties were inactive. From this, we propose that formation of intramolecular hydrogen bonds may lead to radical scavenging activity.

Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies.

The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.

Aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a controlled, randomized trial.

The objective was to assess the efficacy of a biweekly dose of 60 mg aerosolized pentamidine (AP) for primary prophylaxis (PP) of Pneumocystis carinii pneumonia (PCP) and the impact of prophylaxis on survival in HIV-infected patients. Participants were AIDS patients with no history of PCP, patients with a CD4 count < or = 0.200 x 10(9)/L, or patients belonging to the CDC group IVC2, irrespective of CD4 count. It was an open, randomized, controlled trial. Patients were assigned to receive AP, 60 mg biweekly via a System 22 nebulizer, or to a control group not receiving any prophylaxis. Incidence curves for PCP and survival were generated using the Kaplan-Meier method, stratified by treatment group, and compared using the log-rank test. Data were analyzed according to intention to treat. There were 15 cases of PCP among 105 patients in the AP group and 32 cases among 104 patients in the control group. The cumulative incidence of PCP by 18 months was 13% (95% CI 5-21%) in the AP group and 30% (95% CI 18-41%) in the control group, (p = 0.002). During the study period 19 patients (18%) in the AP group died and 24 patients (23%) in the control group (NS; p = 0.28). We conclude that a biweekly dose of 60 mg AP is efficient as primary PCP prophylaxis when a System 22 nebulizer is used. There was, however, no difference in survival between the groups, suggesting that AP has an impact on morbidity only.