Association of Pharmacist Interventions With Adverse Drug Events and Potential Adverse Drug Events.

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs). METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs. RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33. CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.

Identifying factors associated with post-hospital falls in older patients: a territory-wide cohort study.

OBJECTIVES: Post-hospital falls impose a substantial healthcare burden on older adults, yet contributing factors remain inadequately examined. This study aimed to investigate underinvestigated factors associated with post-hospital falls. STUDY DESIGN: Retrospective territory-wide cohort study. METHODS: We examined the electronic medical records of patients aged ≥65 who were discharged from public hospitals in Hong Kong (2007-2018). During the 12 months following discharge, participants were monitored to identify falls based on diagnosis codes or clinical notes from inpatient episodes, the emergency department (ED) visits, and death records. Falls were categorized into two groups: those only requiring ED visits and those requiring hospitalizations. Binary logistic and multinomial logistic regressions examined the associated factors for post-hospital falls and subcategories of falls, respectively. RESULTS: Among 606,392 older patients, 28,593 (4.71%; 95% CI = 4.66%-4.77%) experienced falls within 12 months after discharge. Of those, 8438 (29.5%) only required ED visits, and 20,147 (70.5%) required hospitalizations. Discharge from non-surgical wards, length of stay over two weeks, receiving the Geriatric Day Hospital and Rehabilitation Day Program, advancing age, being female, having more comorbidities, taking more fall risk increasing drugs, previous admission for falls, and living in Hong Kong Island were associated with increased fall risk. Receiving allied health service or nurse service was associated with reduced risk. The same factors were more associated with falls requiring hospitalizations rather than falls only requiring ED visits. CONCLUSIONS: Older patients with identified factors were particularly vulnerable to post-hospital falls leading to rehospitalizations. Fall risk assessment and tailored prevention should prioritize this group.

Tumor resistance to anti-mesothelin CAR-T cells caused by binding to shed mesothelin is overcome by targeting a juxtamembrane epitope.

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.