Short- and long-term impact of a multifaceted approach targeting fluoroquinolone use in a community hospital: an interrupted time-series analysis

International Journal of Clinical Pharmacy - Background While various strategies for antibiotic restrictions have been validated, their impacts are not well described in smaller, non-teaching...     

Rejecting bias: The case against race adjustment for OPO performance in communities of color

In December of 2019, the Centers for Medicare and Medicaid Services (CMS) put out a notice of proposed rule‐making for 42 CFR Part 486, specifically the section that covers the organ procurement organization (OPO) Conditions for Coverage. Most crucially, the proposed rule included two new OPO performance metrics using objective, standardized data from the Centers for Disease Control and Prevention (CDC). These new metrics would employ a denominator that included inpatient deaths from certain causes that could lead to organ donation, rather than the current unverifiable eligible death metric. Although there has been near‐uniform support for replacing the eligible death denominator with CDC data, a source of contention is CMS's proposal not to adjust risk for race in their OPO outcome. Nonetheless, there have been calls for race and ethnicity to be included as risk‐adjusted variables in the CMS donation metric. Herein, we lay out an argument as to why inclusion of race and ethnicity as risk adjustment variables in an OPO performance metric is not only statistically suspect but also will hide the inequities that are detrimental to optimal system performance and assurance that all patients have timely access to donation.     

Duration of use of a levonorgestrel IUS amongst nulliparous and adolescent women

Background

Intrauterine devices are cost-effective if used for 2 or more years. Early discontinuation may lead to reduced cost-effectiveness of this method and unintended pregnancy if other contraceptives are not used. This study sought to examine rates and reasons for discontinuation of IUS use in adolescents versus older women and nulliparous versus parous women, as these groups may be more likely to discontinue use.

Study Design

Retrospective cohort study of women receiving a levonorgestrel IUS between June 2005 and April 2008 was conducted. Medical records were reviewed for all visits following placement of the IUS; rates and reasons for IUS discontinuation were calculated and categorized. Data were examined under two scenarios: (1) assuming that all women not seen for follow-up continued IUS use and (2) only including women with follow-up visits. Cox regression was used to control for age, parity, race and marital status in comparing rates of IUS discontinuation and expulsion in nulliparous versus parous women and adolescents versus older women.

Results

Of the 828 women included in this analysis, 104 (12.6%) were nulliparous, and 131 (15.8%) were ≤20 years of age. Nulliparous women were not more likely than parous women to have expelled their IUS [hazard ratio (95% confidence interval), 1.40 (0.57, 3.43)]. Adolescent women were more likely to experience expulsion than older women, although this did not reach statistical significance [hazard ratio, 1.49 (0.76, 2.92)]. When we looked at reasons for IUS removal, we found that nulliparous women were not more likely than parous women to have their IUS removed because of dissatisfaction with the contraceptive method (6.7% vs. 11.5%, p=.15) or desire to become pregnant (1.9% vs. 2.6%, p=.50). Similarly, adolescents were not more likely than older women to have their IUS removed because of dissatisfaction with the contraceptive method (10.7% vs. 10.9%, p=.94) or desire to become pregnant (3.1% vs. 2.4%, p=.43).

Conclusions

Adolescents and nulliparous women are not more likely to prematurely discontinue use of their IUS than adult or parous women.     

Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity

The role of α(1)-adrenergic receptors (α(1)ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α(1A)AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term α(1A)AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α(1A)AR. CAM-α(1A)AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α(1A)AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-α(1A)AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α(1A)AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-α(1A)AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α(1A)AR mice was 10% longer than that of WT mice. Our results suggest that long-term α(1A)AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.     

Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes

Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.     

MobileMums: A Randomized Controlled Trial of an SMS-Based Physical Activity Intervention

Background  

Postnatal women (<12 months postpartum) are at increased risk of physical inactivity.     

Neonatal quinpirole treatment enhances locomotor activation and dopamine release in the nucleus accumbens core in response to amphetamine treatment in adulthood

Neonatal quinpirole treatment to rats produces long‐term increases in D₂ receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D₂ priming. Male and female Sprague‐dawley rats were administered quinpirole (1 mg kg^?1) or saline from postnatal days (P)1–11. At P60, all animals were given an injection of quinpirole (100 μg kg^?1), and results showed that rats neonatally treated with quinpirole demonstrated enhanced yawning in response to quinprole, verifying D₂ receptor priming because yawning is a D₂ receptor mediated event. Beginning 1–3 days later, locomotor sensitization was tested through administration of d‐amphetamine (1 mg kg^?1) or saline every other day over 14 days, and horizontal activity and turning behavior were analyzed. Findings indicated that D₂‐priming enhanced horizontal activity in response to amphetamine in females compared to males at Days 1 and 4 of locomotor sensitization testing, and D₂‐priming enhanced turning in response to amphetamine. Seven to ten days after sensitization was complete, microdialysis of the NAcc core was performed using a cumulative dosing regimen of amphetamine (0.1–3.0 mg kg^?1). D₂‐primed rats administered amphetamine demonstrated a 500% increase in accumbal DA overflow compared to control rats administered amphetamine. Additionally, amphetamine produced a significant increase in NE overflow compared to controls, but this was unaffected by D₂ priming. These results indicate that D₂ receptor priming as is produced by neonatal quinpirole treatment robustly enhances behavioral activation and accumbal DA overflow in response to amphetamine, which may underlie increases in psychostimulant use and abuse within the psychotic population where increased D₂ receptor sensitivity is a hallmark. Synapse 64:289–300, 2010. © 2009 Wiley‐Liss, Inc.