Pharmacist-Led Deprescribing for Patients With Polypharmacy and Chronic Disease States: A Retrospective Cohort Study.

Background: Current literature and practice have demonstrated that pharmacists have an integral role in deprescribing. However, research regarding their impact on patients with chronic diseases is limited. Objective: To assess the impact of a pharmacist-led intervention on deprescribing inappropriate medication for patients with chronic diseases within a four-month study period compared to patients receiving usual care. Methods: This study was conducted at NYU Langone Health. Patients of the intervention group were referred by a provider and met the criteria of polypharmacy, required chronic disease states management, were nonadherent to medications, had poor health literacy, or required titration for heart failure (HF) guideline directed medical therapy. Results: A total of 142 patients were reviewed over a two-year period. At the end of the study period, the median number of medications for the two respective groups was similar (11 [4 - 30] vs 11 [2 - 23]). The pharmacist-led intervention had on average one medication deprescribed (m = -1.00, sd = 2.57), whereas the control group had on average .44 additional medications (m = 0.44, sd = 3.32) prescribed. Furthermore, the intervention group presented statistically significant differences (P = 0.046) regarding their diastolic blood pressure after the pharmacists' intervention (m = 72.69, sd = 11.64). Most importantly, patients with HF presented statistically significant improvement in their ejection fractions after the intervention (m = 41.46%, sd = 19.28%). Conclusion: The pharmacist-led intervention resulted in significant discontinuation of medications for patients in the intervention group compared to those in the usual care group within four-months.

The Evidence for Antimicrobial and Hard to Infect Regenerative Matrices.

Preparation of the wound bed is a key step in the use of cell- and tissue-based therapy (CTP). In particular, good pre-application debridement is an essential component of CTP. However, there are many situations in which the wound bed is not adequately debrided, including trauma, burn, and in cases of chronic wounds with significant biofilm. In the setting of inadequate wound bed preparation, the use of a CTP that has either added or intrinsic antimicrobial properties is attractive. Some CTPs include added antimicrobial agents such as PHMB or silver, while others have intrinsic antimicrobial components, such as Omega 3 fatty acids. In addition, some wound-covering dressings are completely synthetic, and therefore simply do not become infected. A full understanding of the basic science and clinical data supporting the use of these therapies is important for the advanced wound care practitioner.

The Use of Cellular- and/or Tissue-Based Therapy for the Management of Pyoderma Gangrenosum: A Case Series and Review of the Literature.

Pyoderma gangrenosum (PG) is an uncommon inflammatory neutrophilic disorder with a spectrum of clinical presentations with variable courses. Most cases are associated with an autoimmune disorder and manifest in middle-aged adults as a painful lesion that progresses to painful necrotizing ulcers of the lower extremity. Owing to its variability, clinical diagnosis remains difficult and many patients are often misdiagnosed, with resulting delay in treatment. While early immunosuppressant therapy is key to preventing progression of PG, surgical treatment has been met with criticism because of the risk of potentiating pathergy, an exaggerated skin reaction due to trauma. This article presents a case series in which 3 patients with PG lesions underwent different treatment methods, including surgical debridement and use of fetal bovine dermis (FBD). The use of FBD in conjunction with medical treatment provided pain relief and wound coverage as well as encouraged growth of granulation tissue and long-term stability. Commercial cellular and tissue-based products used to aid in accelerating PG wound closure are also reviewed.

Cystic adventitial disease of the popliteal vein and artery in siblings.

Cystic adventitial disease (CAD) is an uncommon condition in which mucoid cysts form within the adventitial layer of the arterial or venous wall. We have presented two cases in which two first-degree relatives (brother and sister) had acquired CAD ∼6 years apart, one involving the popliteal artery and the other involving the popliteal vein. We have reported a rare case of a possible familial association of CAD. We have discussed the etiology, diagnostic criteria, and imaging modalities between arterial and venous CAD to aid in the management and selection of optimal treatment strategies.

Hydrosurgical Debridement Use Associated With Decreased Surgical Site-Related Readmissions: A Retrospective Analysis.

INTRODUCTION: Debridement is the cornerstone of wound care management. It allows for the removal of fibrinous and necrotic debris from the wound bed as well as the reduction of bacterial bioburden, thus allowing for proper granulation and wound healing. Hydrosurgical debridement uses a controlled, high-pressure fluid jet to cut and remove necrotic debris, contaminants, and bacteria, thereby facilitating a potentially more aggressive debridement. OBJECTIVE: The efficacy of this system was compared with that of other methods of debridement in reducing readmissions due to surgical site infections (SSIs). MATERIALS AND METHODS: Two Current Procedural Terminology codes were used to identify 289 unique patients treated for lower extremity wounds. All patients were treated at a vascular surgery service in a large tertiary care wound program from January 2016 to June 2018. Chart review on wound management was performed. A total of 190 of the 289 patients underwent wound debridement over the course of treatment. Logistic regression was calculated with subsequent SSI admission as the dependent variable. RESULTS: On assessing readmissions owing to SSI following debridement, use of hydrosurgical debridement was found to be associated with decreased SSI admissions (odds ratio, 0.31; 95% CI, 0.142-0.677; P < .05). This finding was compared with the results of either standard sharp soft tissue excisional debridement or the use of pulse irrigation. CONCLUSIONS: There are multiple options to consider when formulating an approach for wound management, including the method of debridement used. One goal of debridement is to decrease the bacterial bioburden in the wound bed to both encourage better wound healing and decrease the rate of wound infections. The present study found that the use of hydrosurgical debridement was associated with decreased SSI readmissions, which could potentially result in better wound care for the patient and possibly decreased health care costs because of a lower rate of readmissions. Further investigation of these 2 potential outcomes is necessary.

The Role of Intermittent Pneumatic Compression in the Treatment of Lower Extremity Chronic Wounds.

Intermittent pneumatic compression devices (IPC) are often used as noninvasive adjuncts in patients with lymphedema, and more recently with venous stasis disease, to promote flow and reduce the adverse effects of interstitial edema associated with both disorders. We will be focusing on lower extremity wounds associated with venous and/or lymphatic disease, the combination often referred to as "lymphophlebitic" disease, and the treatment effect of IPC on this disease process and its sequelae. The function and purpose of pneumatic compression is closely examined along with a variety of pneumatic compression devices that currently exist in the market. A thorough review of the literature was conducted to evaluate the utility of intermittent pneumatic compression in the treatment of lower extremity venous stasis ulcers. Additionally, the author describes personal experience with the use of pneumatic compression on 10 patients with venous stasis ulcers at a single center. There is significant data supporting the use of IPC in patients with lymphophlebitic disease. Overall, ideal patient selection may be crucial. Previous data has shown that patients with high body mass index (>33 kg/m2) and poor functional status (walking less than 200m a day) are related to poor ulcer healing. Therefore, a study that looks primarily at this group (as our small quality assurance [QA] project did) may show increased benefit in this population. It is clear that IPC is of benefit to some patient cohorts with lymphophlebitic disease. This advanced therapy would help patients who have failure of their calf muscle pump and an inability to improve it through other means. However, it is only part of an algorithm that includes: direct wound bed management, moisture control, possible primary venous disease intervention, physical therapy, weight loss, and improved nutrition.

Decreased postoperative pain and opioid use following prepectoral versus subpectoral breast reconstruction after mastectomy: A retrospective cohort study: Pain after pre- versus subpectoral reconstruction.

BACKGROUND: Prepectoral (PP) breast reconstruction is now commonly performed and minimizes dissection of the pectoralis major muscle. Data are lacking comparing the immediate postoperative recovery of these patients as compared with traditional subpectoral (SP) breast reconstruction. METHODS: From December 2015 to February 2017, 73 patients underwent PP prosthetic-based reconstruction at a single academic institution. PP cases were matched 1:1, by age and stage, to patients undergoing traditional SP reconstruction. Analysis of postoperative pain (visual analog scale) and opioid use (oral morphine equivalents, OME), was performed with both bi- and multivariate analyses. Additional outcomes explored included length of stay (LOS) and reconstructive intervention by plane of prosthetic reconstruction. RESULTS: A total of 146 patients were included in the final cohort. PP reconstruction was associated with higher rates of direct-to-implant reconstruction (84.9% vs. 34.3%, p <0.001) and higher rates of initial prosthetic fill (401.53 mL vs. 280.88 mL, p<0.001). Patients undergoing PP reconstruction had significantly reduced postoperative pain (4.29 vs. 5.44, p<0.001) and in-hospital opioid use (62.63 mg OME vs. 98.84 mg OME, p = 0.03) compared with SP patients. This result remained in multivariate analysis for both pain (3.94 vs. 5.25, p<0.001) and opioid use (17.14 mg OME vs. 63.03 mg OME, p = 0.03). Additionally, patients undergoing PP reconstruction had significantly reduced overall LOS on multivariate analysis (21.36 vs. 26.28 h, p = 0.02). CONCLUSION: Following mastectomy, PP breast reconstruction results in significantly reduced pain, opioid use, and hospital LOS compared with SP reconstruction.

Semaglutide: A Novel Oral Glucagon-Like Peptide Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a complex and chronic condition that requires continuous medical care. Uncontrolled hyperglycemia can lead to serious microvascular and macrovascular complications, such as coronary artery disease, peripheral arterial disease, and stroke. Type 2 DM occurs when the pancreas is unable to produce adequate insulin to regulate glucose levels and when there is a decrease in sensitivity to insulin in the body. Insufficient glucagon-like peptide (GLP-1), a normal body hormone, plays an important role in the pathophysiology of DM. The introduction of the GLP-1 receptor agonists expanded therapeutic options in achieving glycemic control in adult patients. In 2005, the US Food and Drug Administration approved exenatide as the first injectable formulation, which led to the advancement of other injectable formulations within the class of GLP-1 receptor agonists. In 2019, semaglutide was approved as the first oral GLP-1 receptor agonist addressing the unmet needs in patients who benefit from therapy with this therapeutic class yet are unwilling to use an injectable drug. This article will provide an overview of the GLP-1 receptor agonists, including the pharmacology of semaglutide, its clinical evidence and role in therapy in type 2 DM.

Cryopreserved Allograft Use in Vascular Surgery.

In vascular surgery, bypass procedures are standard treatments for many arterial and venous diseases. The choice of conduit for the bypass operation is fundamental in planning for the appropriate intervention for each individual patient. Although an autogenous conduit is superior, this option is not available in many patients, and prosthetic grafts have been the preferred conduit in a variety of clinical situations. However, since prosthetic graft infections are seen in all realms of vascular surgery, from arteriovenous access to aortic graft infections and lower-extremity bypass infections, cryopreserved arterial and venous allografts, which are relatively resistant to infection, have become the conduit of choice. This discussion will focus on the clinical applications of cryopreserved allografts in vascular surgery, specifically lower-extremity peripheral bypass, aortic disease, and dialysis access.

Slipped capital femoral epiphysis and Blount disease as indicators for early metabolic surgical intervention.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) and Blount disease are strongly associated with pediatric obesity, yet they have only recently been identified as indications for consideration of metabolic and bariatric surgery (MBS). OBJECTIVES: To describe the relationships between pediatric obesity, MBS, SCFE, and Blount disease. SETTING: Nationwide database. METHODS: The national inpatient sample was used to identify patients ≤20 years old with obesity who underwent MBS from 2007 to 2016. Presence of SCFE and Blount disease was similarly extracted. RESULTS: The overall prevalence of SCFE and Blount disease among patients ≤20 years old is .02% for both (14,976, 11,238 patients, respectively) with no statistically significant change over the study period (P = .68, .07, respectively). The rates of SCFE and Blount disease in children with and without obesity are .46% versus .02% and .36% versus .01%, respectively (P < .001 for both). The mean age of patients with SCFE and obesity was 12 years old, while the mean age of those without obesity was 12.2 years old (P = .03). None of the children with obesity and SCFE underwent MBS. Similarly, the mean age of patients with Blount disease and obesity was 12.6 years old, while the mean age of those without obesity was 13.1 years old. Moreover, the mean age of children with Blount disease and obesity who underwent MBS was 16 years old (P < .001). CONCLUSIONS: Orthopedic complications remain a persistent problem in the pediatric population who suffer from obesity. Despite being diagnosed at a young age, patients with SCFE and/or Blount disease are not undergoing MBS until their later adolescent years, potentially leading to unnecessary disease progression or recurrence of disease after orthopedic interventions. Therefore, SCFE and Blount disease should be considered indications for early consideration of MBS in this pediatric population.

Metabolic differences in breast cancer stem cells and differentiated progeny.

In general, tumor cells display a more glycolytic phenotype compared to the corresponding normal tissue. However, it is becoming increasingly clear that tumors are composed of a heterogeneous population of cells. Breast cancers are organized in a hierarchical manner, with the breast cancer stem cells (BCSCs) at the top of the hierarchy. Here, we investigate the metabolic phenotype of BCSCs and their differentiated progeny. In addition, we determine the effect of radiation on the metabolic state of these two cell populations. Luminal, basal, and claudin-low breast cancer cell lines were propagated as mammospheres enriched in BCSCs. Lactate production, glucose consumption, and ATP content were compared with differentiated cultures. A metabolic flux analyzer was used to determine the oxygen consumption, extracellular acidification rates, maximal mitochondria capacity, and mitochondrial proton leak. The effect of radiation treatment of the metabolic phenotype of each cell population was also determined. BCSCs consume more glucose, produce less lactate, and have higher ATP content compared to their differentiated progeny. BCSCs have higher maximum mitochondrial capacity and mitochondrial proton leak compared to their differentiated progeny. Radiation treatment enhances the higher energetic state of the BCSCs, while decreasing mitochondrial proton leak. Our study indicated that breast cancer cells are heterogeneous in their metabolic phenotypes and BCSCs reside in a distinct metabolic state compared to their differentiated progeny. BCSCs display a reliance on oxidative phosphorylation, while the more differentiated progeny displays a more glycolytic phenotype. Radiation treatment affects the metabolic state of BCSCs. We conclude that interfering with the metabolic requirements of BCSCs may prevent radiation-induced reprogramming of breast cancer cells during radiation therapy, thus improving treatment outcome.

The RNA-binding protein Musashi-1 regulates proteasome subunit expression in breast cancer- and glioma-initiating cells.

Cancer stem cells (CSCs) or tumor-initiating cells, similar to normal tissue stem cells, rely on developmental pathways, such as the Notch pathway, to maintain their stem cell state. One of the regulators of the Notch pathway is Musashi-1, a mRNA-binding protein. Musashi-1 promotes Notch signaling by binding to the mRNA of Numb, the negative regulator of Notch signaling, thus preventing its translation. CSCs have also been shown to downregulate their 26S proteasome activity in several types of solid tumors, thus making them resistant to proteasome-inhibitors used as anticancer agents in the clinic. Interestingly, the Notch pathway can be inhibited by proteasomal degradation of the Notch intracellular domain (Notch-ICD); therefore, downregulation of the 26S proteasome activity can lead to stabilization of Notch-ICD. Here, we present evidence that the downregulation of the 26S proteasome in CSCs constitutes another level of control by which Musashi-1 promotes signaling through the Notch pathway and maintenance of the stem cell phenotype of this subpopulation of cancer cells. We demonstrate that Musashi-1 mediates the downregulation of the 26S proteasome by binding to the mRNA of NF-YA, the transcriptional factor regulating 26S proteasome subunit expression, thus providing an additional route by which the degradation of Notch-ICD is prevented, and Notch signaling is sustained.

Targeted elimination of breast cancer cells with low proteasome activity is sufficient for tumor regression.

Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs), able to regrow a tumor after sublethal treatment while their progeny lack this feature. Furthermore, BCSCs are highly resistant to conventional anticancer treatments. According to the cancer stem cell hypothesis, all cancer stem cells in a tumor have to be eliminated to achieve cancer cure. In this study we tested if targeted elimination of BCSCs leads to tumor regression. Specific targeting of BCSCs was achieved via a unique imaging and targeting system that relies on their low proteasome activity. In our system breast cancer cells stably express a fluorescent fusion protein, thymidine kinase-ZsGreen-cODC, which is readily degraded after translation in cells with normal 26S proteasome activity. However, cells with low proteasome activity accumulate this fluorescent fusion protein, thus allowing for their identification, tracking, and specific elimination. Here, we show that the activity of the 26S proteasome was significantly down-regulated in MCF-7, T47D, and MDA-MB-231 cultures enriched for BCSCs. Treatment with ganciclovir resulted in abrogation of sphere formation in vitro, and tumor regression in vivo, thus demonstrating that targeted elimination of BCSCs leads to loss of self-renewal in vitro and tumor regression in vivo. We conclude that specific targeting of BCSCs could be a useful strategy to improve treatment outcome.

A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction.

Mtb dysregulates monocyte/macrophage functions to produce a large amount of the immunosuppressive cytokine IL-10. An important function of IL-10 in promoting Mtb survival is the suppression of antigen presentation of monocytes/macrophages to T cells. This dampens the host immune responses and provides an opportunity for immune evasion. GSK3 has been shown to control the balance between pro- and anti-inflammatory cytokine productions. Here, we investigated whether GSK3 regulates IL-10 expression and mediates a protective role upon live mycobacterial challenge using BCG as a model. Our results showed that BCG increased Akt phosphorylation and inhibited GSK3 activity, resulting in increased IL-10 production. We confirmed further that suppression of GSK3 activities by a specific chemical inhibitor strongly enhanced BCG-induced IL-10 production. We also showed that IL-10 secreted by BCG-infected human PBMo was a major suppressor of subsequent IFN-gamma production by PBMC and HLA-DR expression on PBMo in response to BCG. Neutralization of PBMo-secreted IL-10 by anti-IL-10 antibodies restored the IFN-gamma production and HLA-DR surface expression. Taken together, GSK3 negatively regulates mycobacteria-induced IL-10 production in human PBMo. The kinase may play a role in restoring IFN-gamma secretions and subsequent antigen presentation in response to mycobacterial infection. In conclusion, our results suggest a significant role for GSK3 in guarding against mycobacterial evasion of immunity via IL-10 induction in the host.

Factors influencing preferences for alternative medicine by Korean Americans.

Use of alternative medicine among the public has increased rapidly over the last few decades. Studies on alternative health care have been conducted on the general public and on major ethnic groups, but not on Korean Americans, who are one of the fastest growing Asian populations in the United States. This study was a cross-sectional survey of 143 Korean Americans in the Greater New York Metropolitan area; all of them were users of alternative medicine. Inter-correlations of hypothetical demographic predictors and preferences for alternative medicine were obtained. Multiple logistic regression analyses were used to identify factors influencing alternative medicine preferences. Most of the respondents answered that they preferred alternative medicine because of philosophical congruence, i.e. they found alternative therapies compatible with their values, world views, spiritual/religious philosophies, and beliefs regarding the nature and meaning of health and illness. The results show that younger, well-educated respondents, with significant acculturation level, and have stayed in the US for a relatively short period of time preferred alternative medicine. The information derived from this and similar studies may be of potential value to the biomedical community, governmental agencies, insurance companies and managed care organizations.

Acculturation and dietary habits of Korean Americans.

This is the first study to investigate how food and nutrient intakes vary with the levels of acculturation of Korean Americans using a dietary assessment tool tested for validity and reliability. The respondents were Korean Americans (n 486) resident in the Greater New York metropolitan area, USA. They were divided into two groups according to the total score of acculturation: low- and high-acculturated groups. Using a food-frequency questionnaire and a modified Suinn-Lew Asian self-identity acculturation scale, differences in the frequencies of food items, food groups and nutrient intakes consumed were analysed by level of acculturation. The low-acculturated group tended to consume significantly more rice, mixed rice, soyabean paste chigae (pot stew), saengsun (fish) chigae, kimchi chigae, other fish broiled or baked, eggs, kimchi, spinach, persimmons, and white or brown sugar in coffee or tea. The high-acculturated group demonstrated a statistically greater tendency to consume bread, cereal, spaghetti, ham, green salad, sweetcorn, chocolate, candies and diet soft drinks. The more acculturated an individual, the more significant was the tendency to consume sweets. The more acculturated group had significantly (P<0.05) higher intakes of % energy from total fat, thiamin, vitamin E and folate, while the low-acculturated group consumed greater amounts of Na, niacin and dietary fibre. The information from the present study can be used to describe dietary habits according to various aspects of acculturation, and allows a better understanding of the dynamics of acculturation and dietary habits.

Development and validation of a food frequency questionnaire for Korean Americans.

A food frequency questionnaire for Korean Americans (KFFQ) was developed by modifying Block's Health Habits and History Questionnaire (HHHQ). The final KFFQ contained 118 food items taking into account culturally specific dietary patterns. Validation of the KFFQ was conducted to compare the nutrient intakes assessed by the KFFQ against those measured by seven-day dietary records in 73 Korean Americans. The mean nutrient values from the KFFQ differed at most by 25% from those of the dietary records with the exception of vitamin A, and 70% of the nutrients (16 out of 23 nutrients) were within 15%. Adjusted Spearman rank-order correlation coefficients for nutrients ranged between 0.45 and 0.84. The overall degree of agreement between the KFFQ and the dietary records was 68% with a range 56% to 79%. This validation study indicates that the KFFQ gives reasonably accurate estimates of the usual dietary intakes among the study population. The results also verify that it is possible to use a FFQ that is both culturally specific and comprehensive with the benefit of being easy to self-administer. This high degree of correlation between the KFFQ and the dietary records demonstrates that the KFFQ provides an easier yet accurate method in large-scale epidemiological studies of relationships between nutrition intakes and diseases in Korean Americans.