Enhancing and Leveraging the West Virginia's Prescription Drug Monitoring Program (PDMP) for Public Health Surveillance and Clinical Decision Making: A Case Study.

West Virginia has struggled with an overdose epidemic for many years and continues to have the highest overdose death rate in the nation. However, through successful collaboration between the West Virginia Board of Pharmacy and the West Virginia Department of Health via its Violence and Injury Prevention Program, West Virginia has improved data quality, enhanced program development and implementation, and developed strategies to address the overdose epidemic. This multiagency collaboration plays an important role in addressing the overdose epidemic and promotes lasting interagency relationships. One strategy is overcoming barriers to maximizing and utilizing the Prescription Drug Monitoring Program, or PDMP. This strategy allows for a better understanding of a patient's prescription history and ensures safer prescribing practices. In addition, this strategic partnership facilitates the use of PDMP data for epidemiologic studies and public health surveillance, which results in sustainable analyses and dissemination of actionable data that are now driving public health action in West Virginia.

Selective internal radiation therapy of metastatic breast cancer to the liver: A meta-analysis.

Introduction: The aim of this study is to conduct a meta-analysis to assess the efficacy of yttrium-90 selective internal radiation therapy (SIRT) in treating patients with breast cancer with hepatic metastasis. Method: PubMed and The Cochrane Library were queried from establishment to January 2021. The following keywords were implemented: "breast", "yttrium", and "radioembolization". The following variables and outcomes were collected: publication year, region, sample size, study design, presence of extrahepatic disease, tumor burden, infused radioactivity, breast cancer subtype, previous treatment, median survival time (MST), length of follow-up, adverse events, and radiographical response such as Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Results: A total of 24 studies from 14 institutions were included in the present meta-analysis. On the basis of the data from 412 patients, post-embolization MST was 9.8 [95% confidence interval (CI): 9.0-11.6] months. Patients with additional extrahepatic metastasis had a poorer survival rate compared with those with localized hepatic metastasis only (MST: 5.3 vs. 15 months, p < 0.0001). Patients with <25% liver tumor burden exhibited more promising survival than those with >25% (MST: 10.5 vs. 6.8 months, p < 0.0139). On the basis of RECIST, mRECIST, and PERCIST criteria, tumor response rate was 36% (95% CI: 26%-47%), 49% (95% CI: 34%-65%), and 47% (95% CI: 17%-78%), respectively, whereas tumor control rate was 85% (95% CI: 76%-93%), 73% (95% CI: 59%-85%), and 97% (95% CI: 91%-100%), respectively. Conclusion: On the basis of the available published evidence, SIRT is feasible and effective in treating patients with breast cancer with liver metastasis. Patients with lower hepatic tumor burden and without extrahepatic metastasis demonstrated more survival benefit. Future randomized controlled trials are warranted.

Facilitators, barriers and lessons learnt from the first state-wide naloxone distribution conducted in West Virginia.

BACKGROUND: Overdose education and naloxone distribution programmes are known to reduce opioid-related deaths. A state-wide naloxone distribution effort of 8250 rescue kits was undertaken by government, community and university partners in West Virginia in 2016-2017. The purpose of this study was to discern the barriers, facilitators and lesson learnt from implementing this endeavour in a rural state with the highest opioid overdose fatality rate in the US. METHODS: Structured interviews (n=26) were conducted among both internal and external stakeholders. Those who participated were >18 years of age and were the lead representative from agencies that either received naloxone (ie, external stakeholders) or helped implement the distribution (ie, internal stakeholders). The interviews followed standardised scripts and lasted approximately 40 min. Sessions were audio-recorded and transcribed. Qualitative content analysis was performed by two researchers to determine themes surrounding facilitators or barriers to programme implementation. RESULTS: The primary facilitators reported by stakeholders included collaborative partnerships, ease of participating in the programme, being established in prevention efforts, demand for naloxone and the need for personal protection from overdose. The primary barriers identified by stakeholders included bureaucracy/policy/procedures of their organisation or agency, stigma, logistical or planning issues, problems with reporting, lack of communication post distribution and sustainability. Numerous lessons were learnt. CONCLUSIONS: Based on the implementation of the programme in 87 organisations, including law enforcement and fire departments, the impact of facilitators outweighed that of barriers. These findings may inform others planning to conduct a similar, large-scale project.

Mechanism of neuromuscular dysfunction in Krabbe disease.

The atrophy of skeletal muscles in patients with Krabbe disease is a major debilitating manifestation that worsens their quality of life and limits the clinical efficacy of current therapies. The pathogenic mechanism triggering muscle wasting is unknown. This study examined structural, functional, and metabolic changes conducive to muscle degeneration in Krabbe disease using the murine (twitcher mouse) and canine [globoid cell leukodystrophy (GLD) dog] models. Muscle degeneration, denervation, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated using the reporter transgenic twitcher-Thy1.1-yellow fluorescent protein mouse. We found that mutant muscles had significant numbers of smaller-sized muscle fibers, without signs of regeneration. Muscle growth was slow and weak in twitcher mice, with decreased maximum force. The NMJ had significant levels of activated caspase-3 but limited denervation. Mutant NMJ showed reduced surface areas and lower volumes of presynaptic terminals, with depressed nerve control, increased miniature endplate potential (MEPP) amplitude, decreased MEPP frequency, and increased rise and decay rate constants. Twitcher and GLD dog muscles had significant capacity to store psychosine, the neurotoxin that accumulates in Krabbe disease. Mechanistically, muscle defects involved the inactivation of the Akt pathway and activation of the proteasome pathway. Our work indicates that muscular dysfunction in Krabbe disease is compounded by a pathogenic mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and a reduction of the Akt pathway. Akt, which is key for muscle function, may constitute a novel target to complement in therapies for Krabbe disease.

Ion channel TRPV1-dependent activation of PTP1B suppresses EGFR-associated intestinal tumorigenesis.

The intestinal epithelium has a high rate of turnover, and dysregulation of pathways that regulate regeneration can lead to tumor development; however, the negative regulators of oncogenic events in the intestinal epithelium are not fully understood. Here we identified a feedback loop between the epidermal growth factor receptor (EGFR), a known mediator of proliferation, and the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), in intestinal epithelial cells (IECs). We found that TRPV1 was expressed by IECs and was intrinsically activated upon EGFR stimulation. Subsequently, TRPV1 activation inhibited EGFR-induced epithelial cell proliferation via activation of Ca2+/calpain and resulting activation of protein tyrosine phosphatase 1B (PTP1B). In a murine model of multiple intestinal neoplasia (Apc(Min/+) mice), TRPV1 deficiency increased adenoma formation, and treatment of these animals with an EGFR kinase inhibitor reversed protumorigenic phenotypes, supporting a functional association between TRPV1 and EGFR signaling in IECs. Administration of a TRPV1 agonist suppressed intestinal tumorigenesis in Apc(Min/+) mice, similar to--as well as in conjunction with--a cyclooxygenase-2 (COX-2) inhibitor, which suggests that targeting both TRPV1 and COX-2 has potential as a therapeutic approach for tumor prevention. Our findings implicate TRPV1 as a regulator of growth factor signaling in the intestinal epithelium through activation of PTP1B and subsequent suppression of intestinal tumorigenesis.

Predictors and complications of blood transfusion in total hip and knee arthroplasty.

Perioperative patient optimization can minimize the need for blood transfusions in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to determine predictors and complications of transfusions. This retrospective review analyzed 1795 patients who underwent primary THA and TKA at our institution between January 2011 and December 2012. Of the 1573 patients ultimately included the rates of transfusion were 9.27% in TKA and 26.6% in THA. Significant predictors for transfusion include: preoperative hemoglobin, age, female gender, body mass index, creatinine, TKA, operating room time, operative blood loss, and intra-operative fluids. The DVT rate was comparable, but deep surgical site infection rate among transfused patients was 2.4% compared to 0.5% in non-transfused patients (P = 0.0065).