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Integrating continuous glucose monitoring into Doctor of Pharmacy curricula
No full textThe use of digital health technology is on the rise. Within diabetes care, continuous glucose monitoring (CGM) is transforming how we monitor and manage patients with diabetes. Pharmacists play pivotal roles in CGM education, accessibility, utility, and application. In turn, pharmacy students should have a working knowledge of these devices. Currently, CGM inclusion in Doctor of Pharmacy (Pharm.D.) curricula is variable, and little is known about the best way to incorporate this content. This article highlights the critical need to intentionally integrate CGM into didactic and experiential teaching. Incorporating CGM education should be individualized to the institution and the level of the trainee. Educational approaches such as patient cases and hands-on activities can enhance CGM-related knowledge, skills, confidence, and empathy, which may empower trainees to be practice-ready and provide essential CGM services after graduation. This guide will provide a suggested framework for integrating CGM into Pharm.D. curricula
Adolescent Social Media Use and Mental Health in the Environmental Influences on Child Health Outcomes Study
No full textPURPOSE: Research on adolescent social media use focuses on negative mental health outcomes, with less attention on potential positive outcomes. The current study addresses this limitation by investigating associations between adolescent social media use and both psychological well-being and psychopathology.
METHODS: Three US-based pediatric cohort sites participating in the National Institutes of Health Environmental influences on Child Health Outcomes study contributed cross-sectional survey data. Adolescents (13-18 years) self-reported the time spent and type of (active, passive) social media use, and their psychological well-being (Patient-Reported Outcome Measurement Information System [PROMIS] Life Satisfaction and Meaning and Purpose), psychopathology (Strengths and Difficulties Questionnaire and PROMIS Depressive Symptoms), and peer relationship quality (PROMIS Peer Relationships). We estimated associations between social media use and 4 mental health groups aligned to the dual factor model of mental health (high well-being/low psychopathology; high well-being/high psychopathology; low well-being/low psychopathology; low well-being/high psychopathology), and tested interactions with peer relationships. Models were adjusted for age, sex, race, ethnicity, and family income.
RESULTS: Participants (N = 963) were sociodemographically diverse (22% income ≤130% federal poverty level; 42% adolescents of color). Elastic net regressions revealed more hours using social media increased the probability of being in the high psychopathology/low well-being group; adolescents with poor peer relationships spending ≥7 hours/day on social media had the greatest risk of poor mental health. Positive peer relationships were the strongest predictor of positive mental health.
DISCUSSION: Peer relationships were the most meaningful contribution to adolescent mental health, and quality of social media use had little influence
Characterisation, management, and outcomes of New Delhi metallo-β-lactamase-producing Escherichia coli: A case series
No full textOBJECTIVE: New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) is a globally growing threat. We sought to describe the microbiology, management and outcomes of patients with this infection at our facility.
METHODS: This is a descriptive case series of patients with NDM-producing Escherichia coli isolated from culture in Detroit between July 2021 and February 2023. Demographics, risk factors, clinical characteristics, management and outcomes were described.
RESULTS: Nine patients were included in the study. Most patients were female with a median age of 67 years. Hepatobiliary disease accounted for 90% of underlying conditions. Nearly all patients had prior antibiotic exposure and the most common specimen source was intra-abdominal fluid. Three patients were not treated due to colonisation; among those treated, the majority received trimethoprim-sulfamethoxazole. The median treatment duration and length of stay were 7 and 15.5 days, respectively. Six (67%) patients survived.
CONCLUSIONS: This report describes a large case series of NDM-producing E. coli infection. Patients with significant comorbidities remain at high risk for CRE infection. Antibiotic options for the treatment of NDM organisms are very limited; new and effective therapies are urgently needed
Labeling and isolating cell specific neuronal mitochondria and their functional analysis in mice post stroke
No full textDendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN(+)) and CaMKIIa positive (CaMKIIa(+)) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke. Neuronal mitochondria were then selectively isolated from the fresh brain tissues excised from the ischemic core (IC), ischemic boundary zone (IBZ), as well as from the homologous contralateral hemisphere (CON) by anti-HA magnetic beads for functional analyses. We found that the bead pulled neuronal specific mitochondria were co-precipitated with GFP and enriched with mitochondrial markers, e.g. voltage-dependent anion channel, cytochrome C, and COX IV, but lacked the Golgi protein RCAS1 as well as endoplasmic reticulum markers: Heme‑oxygenase 1 and Calnexin, indicating that specific neuronal mitochondria have been selectively isolated. Western-blot data showed that oxidative phosphorylation (OXPHOS) components in SYN(+) and CAMKII(+) neuronal mitochondria were significantly decreased in the IBZ and further decreased in the IC compared to the contralateral tissue, which was associated with the significant reductions of mitochondrial function indicated by oxygen consumption rate (OCR) (p \u3c 0.05, respectively, for both neuron types). These data suggest dysfunction of neuronal mitochondria post stroke is present during the stroke recovery stage. Collectively, for the first time, we demonstrated that using a Mito-tag mouse line combined with AAV9 carrying Cre recombinase approach, neuronal specific mitochondria can be efficiently isolated from the mouse brain to investigate their functional changes post stroke
ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma
No full textPURPOSE: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.
METHODS: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m(2) twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles. The primary end point was confirmed objective response rate (ORR; proportion of patients with a ≥20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase) assessed by blinded independent central review (BICR) of volumetric magnetic resonance imaging.
RESULTS: Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term follow-up. Median (range) target PN volumetric best response was -41% (-90 to 13) in adults and -42% (-91 to 48) in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life (HRQOL) that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children.
CONCLUSION: In ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children
How does residency program reputation influence American shoulder and elbow surgeons fellowship match results?
No full textBACKGROUND: Postresidency training is becoming increasingly common among orthopedic surgeons, with shoulder and elbow surgery growing as a desired subspeciality. There is limited data evaluating how the reputation of an applicants\u27 orthopedic residency influences the outcome of the shoulder and elbow fellowship match. The purpose of this study was to determine if applicants from residencies with better reputation have more favorable odds during the match process compared to applicants from residencies with a less prestigious reputation.
METHODS: Residency reputation was determined using the 2023 Doximity residency ranking. These residency programs were then divided into 5 tiers (with tier 1 being the highest ranked and tier 5 being the lowest). Fellowship match data was obtained via San Francisco match from 2016 to 2023. Unmatched applicants, international graduates, and applicants without residency information were excluded. Applicants from 2016 to 2017 were excluded due to incomplete match data. Statistical analysis included descriptive statistics, Chi-square, analysis of variance, and nonparametric analysis.
RESULTS: There was a statistically significant difference with residency tier and average matched rank by fellowship program (P \u3c .001). Applicants from tiers 1, 2, and 3 were more likely to be ranked higher compared to applicants from tiers 4 and 5. Applicants from tier 1 programs sent fewer applications and received a greater proportion of interview offers compared to applicants from tiers 3, 4, and 5 (P \u3c .001). Tier 1 applicants were significantly more likely to be “ranked to match” compared to all remaining applicants (P \u3c .001). There was no significant difference associated with residency tier and match position on the applicant\u27s rank list. However, applicants from tier 1 programs were significantly more likely to match at their top 2 desired programs, compared to applicants from tiers 3, 4, and 5 (P = .029, P = .023, P = .012). Tier 2 applicants were more likely to match at one of their top 2 programs compared to tier 4 and 5 applicants (P = .045, P = .023).
CONCLUSION: Applicants from higher tier residencies are more likely to be ranked higher by shoulder and elbow fellowship programs compared to applicants from lower-tier residencies. Tiers 1, 2, and 3 are ranked approximately equally, while tiers 4 and 5 are ranked significantly lower. There was no association noted between residency tier and applicant match rank; however, applicants from higher-tier residencies were far more likely to match at their top fellowship programs compared to applicants from lower-tier residencies
Guideline Directed Medical Therapies Among Heart Failure Patients Enrolled In Cardiac Rehabilitation
No full textBackground: Heart failure with reduced ejection fraction (HFrEF) guideline-directed medical therapy (GDMT) is lifesaving though medical optimization occurs rarely and slowly. With frequent in-person assessments, cardiac rehabilitation (CR) could be an important opportunity for GDMT optimization. We sought to describe prescribed GDMT among CR enrollees with HFrEF. We hypothesized that GDMT optimization would be low throughout CR. Methods: We queried the University of Michigan EMR and identified patients with most recent (within 12 months) LVEF ≤ 40% and a primary diagnosis of HF who attended CR between January, 2016 and August, 2023. We defined CR cycles as at least 6 CR sessions with no greater than 6 months between consecutive sessions. Using a previously validated algorithm, we generated medication optimization scores (MOS) at the first and final CR session within each cycle. Inputs for the algorithm used data closest to each time point. This included HF GDMT (excluding SGLT2 inhibitors), NYHA classification (assumed NYHA class 2 or 3 HF), systolic BP (SBP), heart rate, creatinine, potassium, allergies, and race we used an SBP cutoff of 100mmHG to define eligibility for titration. The MOS is a percent between 0 (least optimized) and 100 (most optimized). Descriptive statistics were used to summarize population characteristics, and Wilcoxon Signed-Rank analysis was used to compare MOSs at the start and end of CR. Results: 172 CR cycles were completed by 152 patients (63.8% male, 78.3% White, mean age 67.5 [SD 12.1] years), including 18 patients who completed 2 CR cycles and 2 who completed 3 CR cycles (Table 1). The mean number of sessions per CR cycle was 26.3 (SD 10.6). At the end of CR, 85 (49.4%) patients were on a beta-blocker, 84 (48.8%) an ACE inhibitor/ARB/ARNI, and 31 (18.0%) an MRA. After accounting for contraindications to GDMT, patients were eligible for initiation or uptitration of at least 1 class of GDMT at the end of 144 (83.7%) CR cycles (Table 1). The median MOS at the start of CR was 39% (IQR 14 - 57) and at the end of CR was 35% (IQR 14 - 57) (p= 0.79). Conclusion: GDMT utilization among patients with HFrEF participating in CR is suboptimal and does not improve over time in routine practice. There is substantial opportunity to develop and validate strategies to improve GDMT prescribing during CR
Patient-Reported Outcomes: Comparing Functional Avoidance and Standard Thoracic Radiation Therapy in Lung Cancer
No full textPURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.
METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline and percentage of clinically meaningful declines were calculated. We compared results against PROs from RTOG 0617 and PACIFIC trial data using Student t-tests and chi-square tests.
RESULTS: Fifty-nine patients completed baseline PRO surveys. The median age was 65 (44-86) years, non-small cell lung cancer comprised 83%, and median dose was 60 Gy in 30 fractions. The percent of patients with clinically meaningful decline in FACT-TOI at 12 months was 47.8% for RTOG 0617% and 26.8% for functional avoidance (P = .03). The functional avoidance cohort demonstrated a significantly (P = .012) higher change in EQ-VAS score at 12 months (9.9 ± 3.3; average ± SE) compared with the PACIFIC cohort (1.6 ± 0.6).
CONCLUSION: The current work demonstrates improved PROs from a phase II functional avoidance trial in certain subscales (FACT-TOI and EQ-VAS) compared with PROs from seminal studies (RTOG 0617 and PACIFIC). The presented data support investigation of 4DCT functional avoidance in a phase III setting
Bioengineered vessels used for vascular repairs in trauma
No full textClinical trials demonstrate favorable outcomes of bioengineered vessels as graft conduits for reparation of traumatic vascular injuries compared with benchmarked synthetic conduits
Surgery versus radiation for clinically positive nodal prostate cancer in an other cause mortality risk weighted cohort
No full textPURPOSE: This study examined cancer control metrics between surgery and radiation for clinically positive nodal prostate cancer in an other-cause mortality weighted cohort, to circumvent limitations in previous studies.
METHODS: The Surveillance, Epidemiology, and End Results Research Plus database was queried to identify men with clinically positive nodal prostate cancer at diagnosis between 2004 and 2017 who were treated with surgery or radiation. A competing-risks regression model was used to calculate the 10-year other-cause mortality risk using available covariates, including treatment type. Inverse probability of treatment weighting was then used to balance covariates, including other-cause mortality risk. Then, competing-risks cumulative incidence curves and multivariable models, which were weighted on the calculated other-cause mortality risk, were used to examine the impact of treatment type on cancer-specific mortality, after accounting for covariates.
RESULTS: 4739 patients underwent surgery whereas 1039 underwent radiation. The median follow-up was 4.7 years (2.6-8.2). Other-cause mortality was statistically different between treatment arms in the unweighted cohort (Gray\u27s p = 0.005), but that difference disappeared in the weighted cohort (Gray\u27s p = 0.2). At 10 years, the cancer-specific mortality rate was 27.6% (22.2-33.9) for radiation versus 18.1% (16.2-20.3) for surgery (p \u3c 0.001). On competing-risks multivariable analysis, radiation had 1.86-fold (95% CI 1.69-2.12) higher hazard likelihood from one year to the next compared to surgery (p \u3c 0.001).
CONCLUSION: Clinically positive nodal patients treated with radiation fare worst cancer-specific mortality than those that underwent surgery, using calculated other-cause mortality risk