Paliperidone to treat psychotic disorders

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysreg-ulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

HIV-1-infected individuals harbor a latent reservoir of infected CD4⁺ T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from the latent reservoir showed gp160 env sequences that were identical to at least one other virus. Moreover, 43% of the env sequences from viruses emerging from the reservoir were part of identical groups at the two time points. Groups of identical expanded sequences made up 54% of proviral DNA, and, as might be expected, the sequences of replication-competent viruses in the active reservoir showed limited overlap with integrated proviral DNA, most of which is known to represent defective viruses. Finally, there was an inverse correlation between proviral DNA clone size and the probability of reactivation, suggesting that replication-competent viruses are less likely to be found among highly expanded provirus-containing cell clones

Safety, tolerability, pharmacokinetics, and immunological activity ...

This phase 1 study showed the feasibility of combining anti-HIV bnAbs targeting different sites on the HIV envelope in people living without HIV. It also showed that the dual-antibody and triple-antibody combinations were as effective as the individual antibodies at neutralisation, thus justifying a combination approach going forward for additional monoclonal antibody studies for HIV prevention. The fact that modelling predicted the combination neutralisation titre on the basis of the single antibody titres will be valuable for future trial design of different antibody combinations

The Effect of Booster Seat Use on Pediatric Injuries in Motor Vehicle Frontal Crashes

Background: Motor vehicle crashes are a significant source of pediatric mortality and morbidity. Studies indicate that booster seats significantly improve seat belt fit for children who have not attained a height of 145 cm (4’ 9”). This study examined injuries occurring in booster age children up to age 12, as the majority of children do not attain 145 cm until this age. The purpose of the study was to identify differences in injuries due to the type of restraint used, with attention to musculoskeletal injuries. Methods: Vehicle and occupant data were obtained from a publically available statistical sample of tow-away crashes. Frontal crashes over an 8-year period were examined. A data set of cases was created involving children ages 5 to 12 years who were unrestrained, restrained using the vehicle’s lap and shoulder belt, and restrained using a booster seat with the vehicle’s lap and shoulder seat belt. Injury severity, frequency, and patterns of distribution were compared. Results: Unrestrained children experienced moderate to severe injuries 3.8 to 19 times more frequently than children using restraints. There were more injuries to the head and face in unrestrained versus restrained children, but the head and face was the most frequently injured region for all groups. There were no serious cervical spine injuries reported for any group. Lower extremity fractures were not observed in booster seat users but occurred at similar rates in both unrestrained and seat belt restrained children. These fractures occurred in older children who were involved in more severe crashes. Conclusions: Unrestrained children were more likely to experience moderate and severe injuries than restrained children. The data sample suggests that booster use may reduce the risk of extremity fracture, as there were no extremity fractures in children restrained with booster seats. Clinical Relevance: This work provides evidence for the efficacy of booster use for preventing orthopaedic injury in children. This evidence can be used to inform parents and establish recommendations for best practices in transporting children

The Effect of Booster Seat Use on Pediatric Injuries in Motor Vehicle Frontal Crashes

Background: Motor vehicle crashes are a significant source of pediatric mortality and morbidity. Studies indicate that booster seats significantly improve seat belt fit for children who have not attained a height of 145 cm (4’ 9”). This study examined injuries occurring in booster age children up to age 12, as the majority of children do not attain 145 cm until this age. The purpose of the study was to identify differences in injuries due to the type of restraint used, with attention to musculoskeletal injuries. Methods: Vehicle and occupant data were obtained from a publically available statistical sample of tow-away crashes. Frontal crashes over an 8-year period were examined. A data set of cases was created involving children ages 5 to 12 years who were unrestrained, restrained using the vehicle’s lap and shoulder belt, and restrained using a booster seat with the vehicle’s lap and shoulder seat belt. Injury severity, frequency, and patterns of distribution were compared. Results: Unrestrained children experienced moderate to severe injuries 3.8 to 19 times more frequently than children using restraints. There were more injuries to the head and face in unrestrained versus restrained children, but the head and face was the most frequently injured region for all groups. There were no serious cervical spine injuries reported for any group. Lower extremity fractures were not observed in booster seat users but occurred at similar rates in both unrestrained and seat belt restrained children. These fractures occurred in older children who were involved in more severe crashes. Conclusions: Unrestrained children were more likely to experience moderate and severe injuries than restrained children. The data sample suggests that booster use may reduce the risk of extremity fracture, as there were no extremity fractures in children restrained with booster seats. Clinical Relevance: This work provides evidence for the efficacy of booster use for preventing orthopaedic injury in children. This evidence can be used to inform parents and establish recommendations for best practices in transporting children

Abstract Number ‐ 183: pcASPECTS can help predict clinical outcome in basilar artery occlusion strokes who undergo endovascular thrombectomy

Introduction Basilar artery occlusion (BAO) is a life‐threatening condition associated with high morbidity and mortality. The clinical effectiveness of endovascular therapy (EVT) in patients with stroke due to BAO is not well established. The objective of our study is to investigate the role of Posterior circulation Acute Stroke Prognosis Early CT Score (pcASPECTS) in predicting clinical outcome in patients with BAO who undergo EVT. Methods We conducted a retrospective analysis on 45 patients with acute BAO who received EVT from November 2015 to June 2022. Information was collected on demographic variables, medical history, clinical parameters, and CT based pcASPECTS on admission. Functional outcomes were assessed via binarization of the following variables: the modified Rankin scale score on discharge, NIH stroke scale on discharge, and the modified Rankin scale score 90 days following discharge. A series of logistic regression models adjusted for age, gender, atrial fibrillation, systolic blood pressure at admission, tPA receipt, and NIH stroke scale on admission were run to assess the association of pcASPECTS score on admission with binarized outcome measures. Results Among 45 patients (mean age 63.6+11.4 years, 73.3% males), binarized pcASPECTS score on admission (7: lower severity) was not shown to be significantly associated with functional outcome across a series of logistic regression models. When assessing for binarized modified Rankin scale at discharge (0‐3: good outcome, 4–6: poor outcome), a lower severity of pcASPECTS showed 5.47 times the odds of a good outcome (OR: 5.47; 95% CI: 0.17, 173.25; p‐value: 0.34). When assessing for binarized NIH stroke scale on discharge (0‐15: mild/moderate; >15: severe), a lower severity pcASPECTS showed 6.05 times the odds of a mild/moderate outcome as opposed to a severe outcome (OR: 6.05; 95% CI: 0.32, 114.62; p‐value: 0.23). When assessing for a modified Rankin scale at 90 days post‐discharge, binarized as above, a lower severity pcASPECTS showed 4.36 times the odds of a good outcome (OR: 4.36; 95% CI: 0.27, 69.40; p‐value: 0.30). Conclusions Our study revealed that pcASPECTS on admission may help predict clinical outcomes in patients receiving EVT for BAO and therefore could be used as a guide for medical and endovascular management. These findings have far‐reaching applicability but will require larger studies to confirm significant clinical benefit