Birgitte Nybo Jensen

Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis.

Bronchoalveolar lavage (BAD cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients with Pneumocystis carinii pneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PGP who survived (P = 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P = 0.0007).

Pulmonary pathogens in HIV-infected patients.

On well defined criteria a total of 102 fiberoptic bronchoscopies (FB) were done on HIV-infected patients with pulmonary symptoms. A microbiological agent was identified in 85 patients (83%). Pneumocystis carinii (PC) was histologically verified in 61 patients, bacteria cultured in 22 patients, and cytomegalovirus (CMV) cultured in 17 patients. A histological diagnosis of CMV was only established in 2/17 patients. In the present study, a CMV positive culture from bronchial lavage fluid did not appear related to the clinical picture. Patients with P. carinii pneumonia (PCP) had significantly higher IgA, lower CD4-count, more commonly dyspnea and an X-ray showing diffuse interstitial infiltration than patients without PCP. Patients with bacterial pneumonia had significantly higher CD4-count, lower IgA, more commonly productive cough and an X-ray showing focal infiltration. In more than 75% of the patients, microorganisms identified were responsible for the pulmonary symptoms leading to bronchoscopy. Mainly PC and bacterial pathogens, both of which are treatable, were responsible for these infections. Pulmonary infections of clinical relevance besides PCP and bacterial infections were rare (3%, 95% confidence limit 1-8%).

Randomized Study of Sulfamethoxazole-trimethoprim versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis carinii Pneumonia in Patients with AIDS

In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP) against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94 patients participated in the study, 47 in each group. The patients were observed for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while 1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was 9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX-TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX-TMP. Furthermore, we found a tendency towards a protective effect against toxoplasmosis in the SMX-TMP group, though there was no difference in survival between the two groups. There was no statistical difference in frequency of crossover from one therapy form to the other. Based on these data we recommend SMX-TMP for secondary PCP prophylaxis.

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.

Time-related Decrease in Diffusion Capacity in HIV-infected Patients with Impaired Immune Function

The purpose of this study was to investigate acute and time-related changes in lung function, i.e. forced expiratory volume in 1 second (FEV1), vital capacity (VC) and transfer factor (KCO) in HIV-infected patients with CD4 cell counts less than 400 x 10(6)/l. 66 males with no history of HIV-related pulmonary symptoms participated in a prospective lung function study for 9 months with 3-month intervals between examinations. 15/66 patients (23%) developed acute pulmonary symptoms, i.e. dyspnea (n = 12), cough (n = 13), fever greater than 38 degrees C (n = 13) and interstitial infiltrates on the X-ray (n = 9). Among the 51 asymptomatic patients, a significant time-related decrease in KCO (median decrease of 7%) was found, whereas no significant change in FEV1 or VC was observed during the study. Baseline KCO, i.e. KCO at entry, was found to be significantly higher in the asymptomatic patients (102% predicted (pred.) than in those patients who developed pneumonia (88% pred.). Development of pulmonary symptoms was both followed by a significant decrease in KCO (median decrease 17%), FEV1 and VC. We therefore conclude that HIV-infected patients with impaired immune function have in the absence of pulmonary symptoms a decrease in KCO. In case of pneumonia an acute decrease in both KCO, FEV1 and VC occurs.

Prevention of pneumocystis carinii pneumonia relapse by aerosolised pentamidine, 60 mg biweekly, using an acorn system 22 nebuliser

The effectiveness of biweekly administration of 60 mg aerosolised pentamidine (AP) as secondary prophylaxis against relapse of Pneumocystis carinii pneumonia (PCP) was investigated in 45 male AIDS patients. The nebuliser used was an Acorn System 22. In total the patients received AP for a mean period of 13.8 months (3.4-28.8). Six episodes of recurrent PCP were recorded. Relapse per full year of treatment on AP was 12%.

Important Aspects of Pharmacist-led Medication Reviews in an Acute Medical Ward

In some hospitals, clinical pharmacists review the medication to find drug‐related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review (MR) notes, we retrospectively evaluated the clinical implementation and classified (1) timing and communication of the review; (2) DRPs and related suggestions for the physician; and (3) DRPs’ potential clinical relevance to patients as ‘beneficial’, ‘somewhat beneficial’, ‘no relevance’ or ‘other relevance’. Of 327 DRPs (0–13 DRPs per patient), 42% were implemented. The clinical implementation was higher if the MR note was made prior to (instead of after) the physicians admission, and even higher if the suggestions were communicated verbally (instead of only in writing) to the physicians (44% versus 79%, p < 0.05). The clinical relevance of the DRPs was either ‘beneficial’ (16%), ‘somewhat beneficial’ (43%), ‘no relevance’ (22%) or ‘other relevance’ (19%). The ‘beneficial’ DRPs had a higher clinical implementation (53%) than ‘no relevance’ (34%) (p < 0.05). The most frequently implemented suggestions were based on DRPs concerning ‘indication for drug treatment not noticed’, ‘inappropriate drug form’ and ‘drug dose too low’, with implementation rates of 83%, 67% and 63%, respectively. In our sample, the pharmacists MR suggestions were only implemented by physicians in 42% of the cases, but review prior to physician contact and verbal communication of the suggestions, higher clinical relevance and specific types of DRPs were associated with a higher implementation rate.