Antipsychotic drug use and risk of pneumonia in elderly people

OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people.DESIGN: A nested case-control analysis.SETTING: Data were used from the PHARMO database, which collates information from community pharmacies and hospital discharge records.PARTICIPANTS: A cohort of 22,944 elderly people with at least one antipsychotic prescription; 543 cases of hospital admission for pneumonia were identified. Cases were compared with four randomly selected controls matched on index date.MEASUREMENTS: Antipsychotic drug use in the year before the index date was classified as current, recent, or past use. No prescription for an antipsychotic in the year before the index date was classified as no use. The strength of the association between use of antipsychotics and the development of pneumonia was estimated using multivariate logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Current use of antipsychotics was associated with an almost 60% increase in the risk of pneumonia (adjusted OR=1.6, 95% CI=1.3-2.1). The risk was highest during the first week after initiation of an antipsychotic (adjusted OR=4.5, 95% CI=2.8-7.3). Similar associations were found after exclusion of elderly people with a diagnosis of delirium. Current users of atypical agents showed a higher risk of pneumonia (adjusted OR=3.1, 95% CI=1.9-5.1) than users of conventional agents (adjusted OR=1.5, 95% CI=1.2-1.9). There was no clear dose-response relationship.CONCLUSION: Use of antipsychotics in elderly people is associated with greater risk of pneumonia. This risk is highest shortly after the initiation of treatment, with the greatest increase in risk found for atypical antipsychotics.</p

Genetic Variation and the Risk of Haloperidol-Related Parkinsonism in Elderly Patients A Candidate Gene Approach

<p>Factors that influence the variation in occurrence of antipsychotic-related parkinsonism in elderly have not been well elucidated. The aim of this study was to investigate whether previous identified and studied genetic polymorphisms at DRD2, ANKK1, DRD3, HTR2A, HTR2C, RGS2, COMT, and BDNF genes are associated with antipsychotic-related parkinsonism in elderly patients.</p><p>This cross-sectional study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. The investigated predictors were polymorphisms in DRD2 (141CIns/Del and C957T), ANNK1 (TaqIA), DRD3 (Ser9Gly), HTR2A (-1438G>A and His452Tyr), HTR2C (Cys23Ser and -759C/T), RGS2 (+2971C>G), COMT (G158A), and BDNF (Val66Met). Frequencies of the -759 T allele of the HTR2C gene and the 158A allele of the COMT gene were significantly higher in patients without antipsychotic-induced parkinsonism (AIP) (nominal P = 0.03 and P = 0.02, respectively). -759 T allele carriership in females was associated with a lower risk of AIP (adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.85). The decrease in risk of AIP in carriers of the COMT 158A allele did not reach statistical significance. No significant associations were found between AIP and the remaining selected polymorphisms.</p><p>Although validation is needed, this study suggests that carriership of the -759 T allele of the HTR2C gene in females may be protective against development of parkinsonism in elderly patients during treatment with haloperidol.</p>

Daily intranasal palivizumab to prevent respiratory syncytial virus infection in healthy preterm infants: a phase 1/2b randomized placebo-controlled trialResearch in context

Summary: Background: Mucosal administration of monoclonal antibodies (mAbs) against respiratory pathogens is a promising alternative for systemic administration because lower doses are required for protection. Clinical development of mucosal mAbs is a highly active field yet clinical proof-of-concept is lacking. Methods: In this investigator-initiated, double-blind, randomized placebo-controlled trial, we evaluated intranasal palivizumab for the prevention of RSV infection in preterm infants (Dutch Trial Register NTR7378 and NTR7403). We randomized infants 1:1 to receive intranasal palivizumab (1 mg/mL) or placebo once daily during the RSV season. Any RSV infection was the primary outcome and RSV hospitalization was the key secondary outcome. The primary outcome was analyzed with a mixed effect logistic regression on the modified intention-to-treat population. Findings: We recruited 268 infants between Jan 14, 2019 and Jan 28, 2021, after which the trial was stopped for futility following the planned interim analysis. Adverse events were similar in both groups (22/134 (16.4%) palivizumab arm versus 26/134 (19.4%) placebo arm). There were 6 dropouts and 168 infants were excluded from the efficacy analyses due to absent RSV circulation during the SARS-CoV-2 pandemic. Any RSV infection was similar in infants in both groups (18/47 (38.3%) palivizumab arm versus 11/47 (23.4%) placebo arm; aOR 2.2, 95% CI 0.7–6.5). Interpretation: Daily intranasal palivizumab did not prevent RSV infection in late preterm infants. Our findings have important implications for the clinical development of mucosal mAbs, namely the necessity of timely interim analyses and further research to understand mucosal antibody half-life. Funding: Funded by the Department of Pediatrics, University Medical Centre Utrecht, the Netherlands