Optimizing therapy to prevent avoidable hospital admissions in multimorbid older adults (OPERAM): cluster randomised controlled trial

OBJECTIVETo examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital.DESIGNCluster randomised controlled trial.SETTING110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors.PARTICIPANTS2008 older adults (>= 70 years) with multimorbidity (>= 3chronic conditions) and polypharmacy (>= 5 drugs used long term).INTERVENTIONClinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing.MAIN OUTCOME MEASUREPrimary outcome was first drug related hospital admission within 12 months.RESULTS2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had >= 1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths).CONCLUSIONSInappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes.Algorithms and the Foundations of Software technolog

Poly(ADP-ribose) polymerase (PARP) revisited. A new role for an old enzyme: PARP involvement in neurodegeneration and PARP inhibitors as possible neuroprotective agents

PolyADP-ribosylation can, in turn, modify the activities of various proteins. PAW has been shown to be activated by nicks in the DNA molecule and to be involved in DNA plasticity-related phenomena such as DNA repair, carcinogenesis, cell proliferation and gene expression. PARP inhibitors, such as benzamide, have been shown to differently affect the long-term survival of different cell types subjected to varying insults. For example, benzamide can increase the mortality of glucocorticoid-treated mouse lymphoma cells, while it can also prevent the death of a murine macrophage tumor cell line exposed to hydrogen peroxidation. The first part of the present series of studies was undertaken to investigate the possible involvement of PARP in glutamate-induced neurotoxicity in cerebellar granule cells in vitro, and the effects of PAW inhibitors on the survival of these neurons. In the second part of the study, the in vivo effects of PARP inhibitors on MPTP-induced catecholamine neurotoxicity in C57B1/6N mice were examined. Although these compounds might act at other sites in addition to PAW, the results of our studies indicate that PARP inhibitors possess neuroprotective potential in vivo and suggest a role of PARP in MPTP neurotoxicity