Effectiveness of an evidenced-based cognitive behavioral therapy intervention for adolescents in a school setting.

PROBLEM: The adolescent years are a formative time when rapid hormonal and physical changes stimulate the developing mind. Exposure to poverty, abuse, violence, and lack of peer and social support causes an increase in vulnerability to the development of mental health problems. The COVID-19 pandemic has also exacerbated symptoms of depression and anxiety. Regardless of the risk factors, anxiety and depression continue to be significant health problems, affecting thousands of adolescents yearly in the United States. The first-line treatment recommendation for managing anxiety and depression symptoms is cognitive behavioral therapy (CBT). However, access to a provider for CBT treatment is not always an option for many reasons. METHODS: This pilot evidenced-based practice project aims to increase access to skills acquired through CBT and improve adolescents' mental health by implementing a brief and evidenced-based CBT program in a school setting. The CBT program for this project is the Creating Opportunities for Personal Empowerment (COPE) for Teens program consisting of seven 50-55-min sessions. The COPE program was delivered to 22 students in a 7th-grade health class. The Generalized Anxiety Disorder 7-Item and Patient Health Questionnaire-9 Modified for Adolescents measured anxiety and depression scores at baseline, post-intervention, and 2-month follow-up. FINDINGS: Results indicate clinically significant improvements in anxiety and depression scores and showed participant satisfaction. CONCLUSIONS: COPE in the school setting offers a low-risk solution to improving behaviors and emotional intelligence. COPE is a cost-effective solution to the mental health provider shortage.

A global examination of clinical ladder programs - A synthesis of commonalities and opportunities for standardization.

BACKGROUND: Clinical ladder programs (CLPs) have been part of the nursing profession for nearly 4 decades. However, the structure and implementation of CLPs vary widely throughout healthcare systems. CLPs are a valuable factor in nurse retention and employee satisfaction initiatives, but globally replicating and measuring their impact is difficult due to lack of standardization. AIM: To identify opportunities for global standardization of CLPs through a systematic review of published evidence and facility-sourced CLPs applications and program documents. METHOD: This study used a systematic literature search and scan of existing programs from facilities within the United States (US), Lebanon, and Ghana obtained through professional ties and organizational membership. RESULTS: Seventy-nine articles were screened with 30 studies identified for inclusion, plus 20 CLPs from the US and international facilities. Identified commonalities were the lack of consistency in the number of clinical levels across the CLPs, eligibility requirements and application process, reward and recognition, lack of emphasis on technology and informatics, and missed opportunities to use CLPs to drive a culture of safety. The administrative burden of the programs and the time required by the nurse to complete the CLP application were rarely referenced. LINKING EVIDENCE TO ACTION: The lack of consistency between facilities and across the healthcare sectors limits the measurable impact CLPs have on the nursing profession. Recommendations for practice include developing a standardized professional development framework. A standardized framework will encourage adoption of a retention tool that will provide the profession with a measurable method to demonstrate the value it brings to patient care. Providing guidance to health care facilities in low- and middle-income countries on the implementation of a professional development framework will assist in closing the global gap of professional development opportunities for nurses.

Safety and efficacy of a hybrid approach for repair of complicated aberrant subclavian arteries.

OBJECTIVE: Aberrant subclavian artery (ASA), a well-described aortic arch anomaly, is frequently associated with dysphagia and development of Kommerell diverticulum (KD) with aneurysmal degeneration. Historically, open repair has been performed, which can be associated with significant morbidity. More recently, hybrid approaches using different arch vessel revascularization techniques in combination with thoracic endovascular aortic repair (hybrid TEVAR) have been described, but there is a paucity of literature describing outcomes. The objective of this analysis was to describe our experience with management of complicated ASAs using hybrid TEVAR, further adding to the literature describing approaches to and outcomes of hybrid ASA repair. METHODS: A retrospective, single-institution review was performed of all patients treated for ASA complications using hybrid TEVAR (2002-2018). The primary end point was technical success, defined as absence of type I or type III endoleak intraoperatively and within 30 days postoperatively. Secondary end points included complications, reintervention, and survival. Centerline measurement of KD diameters (maximum diameter = opposing aortic outer wall to diverticulum apex) was employed. Kaplan-Meier methodology was used to estimate secondary end points. RESULTS: Eighteen patients (1.4% of 1240 total TEVAR procedures; male, 67%; age, 59 ± 13 years) were identified (left-sided arch and right ASA, 94% [n = 17]; right-sided arch and left ASA, n = 1 [6%]; retroesophageal location and associated KD, 100%); median preoperative KD diameter was 60 mm (interquartile range [IQR], 37-108 mm). Operative indications included diverticulum diameter (61%), dysphagia (17%), rupture (11%), rapid expansion (6%), and endoleak after TEVAR (6%). All procedures used some combination of supraclavicular revascularization and TEVAR (staged, 50% [n = 9]), whereas partial open arch reconstruction was used in 17% (n = 3). There were no perioperative deaths or spinal cord ischemic events. Major complications occurred in 22% (n = 4): nondisabling stroke, one; arm ischemia, one; upper extremity neuropathy, one; and iatrogenic descending thoracic aortic dissection, one. Technical success was 83%, but 44% (n = 8) had an endoleak (type I, n = 3; type II, n = 5 [intercostal, n = 2; aneurysmal subclavian artery origin, n = 3]) during follow-up (median, 4 months; IQR, 1-15 months). Two endoleaks resolved spontaneously, three were treated, and three were observed (1-year freedom from reintervention, 75% ± 10%). Median KD diameter decreased by 7 mm (IQR, 1-12 mm), and 78% (n = 14) experienced diameter reduction or stability in follow-up. The 1- and 3-year survival was 93% ± 6% and 84% ± 10%, respectively. CONCLUSIONS: Hybrid open brachiocephalic artery revascularization with TEVAR appears to be safe and reasonably effective in management of ASA complications as evidenced by a low perioperative complication risk and reasonable positive aortic remodeling. However, endoleak rates raise significant concerns about durability. Therefore, if this technique is employed, the mandatory need for surveillance and high rate of reintervention should be emphasized preoperatively. This analysis represents a relatively large series of a hybrid TEVAR technique to treat ASA complications, but greater patient numbers and longer follow-up are needed to further establish the role of this procedure.

Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics.

Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks. CKD was confirmed by measurements of glomerular filtration rate, blood urea nitrogen, and kidney histopathology. Mice with CKD displayed lower muscle force production and greater ischemic lesions in the tibialis anterior muscle (78.1 ± 14.5% vs. 2.5 ± 0.5% in control mice, P < 0.0001, N = 5-10/group) and decreased myofiber size (1661 ± 134 µm2 vs. 2221 ± 100 µm2 in control mice, P < 0.01, N = 5-10/group). This skeletal myopathy occurred despite normal capillary density (516 ± 59 vs. 466 ± 45 capillaries/20x field of view) and limb perfusion. CKD mice displayed a ~50-65% reduction in muscle mitochondrial respiratory capacity in ischemic muscle, whereas control mice had normal mitochondrial function. Hydrogen peroxide emission was modestly higher in the ischemic muscle of CKD mice, which coincided with decreased oxidant buffering. Exposure of cultured myotubes to CKD serum resulted in myotube atrophy and elevated oxidative stress, which were attenuated by mitochondrial-targeted therapies. Taken together, these findings suggest that mitochondrial impairments caused by CKD contribute to the exacerbation of ischemic pathology.

The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

PURPOSE: Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis. METHODS: A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable. RESULTS: During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities. CONCLUSIONS: Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial.

BACKGROUND: The purpose of the study was to compare the effectiveness of olanzapine (OLN) and aprepitant (APR) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy. METHODS: A phase III trial was performed in chemotherapy-naive patients receiving cisplatin ≥ 70 mg/m(2) or cyclophosphamide ≥ 500 mg/m(2) and doxorubicin ≥ 50 mg/m(2), comparing OLN to APR in combination with palonosetron (PAL) and dexamethasone (DEX). The OLN, PAL, DEX (OPD) regimen was 10 mg of oral OLN, 0.25 mg of IV PAL, and 20 mg of IV DEX prechemotherapy, day 1, and 10 mg/day of oral OLN alone on days 2-4 postchemotherapy. The APR, PAL, DEX (APD) regimen was 125 mg of oral APR, 0.25 mg of IV PAL, and 12 mg of IV DEX, day 1, and 80 mg of oral APR, days 2 and 3, and 4 mg of DEX BID, days 2-4. Two hundred fifty-one patients consented to the protocol and were randomized. Two hundred forty-one patients were evaluable. RESULTS: Complete response (CR) (no emesis, no rescue) was 97% for the acute period (24 hours postchemotherapy), 77% for the delayed period (days 2-5 postchemotherapy), and 77% for the overall period (0-120 hours) for 121 patients receiving the OPD regimen. CR was 87% for the acute period, 73% for the delayed period, and 73% for the overall period in 120 patients receiving the APD regimen. Patients without nausea (0, scale 0-10, MD Anderson Symptom Inventory) were OPD: 87% acute, 69% delayed, and 69% overall; APD: 87% acute, 38% delayed, and 38% overall. There were no grade 3 or 4 toxicities. CR and control of nausea in subsequent chemotherapy cycles were equal to or greater than cycle 1 for both regimens. OPD was comparable to APD in the control of CINV. Nausea was better controlled with OPD. DISCUSSION: In this study, OLN combined with a single dose of DEX and a single dose of PAL was very effective at controlling acute and delayed CINV in patients receiving highly emetogenic chemotherapy. CR rates were not significantly different from a similar group of patients receiving highly emetogenic chemotherapy and an antiemetic regimen consisting of APR, PAL, and DEX.

Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

Analysis of FHIT allelic imbalance/loss of heterozygosity and FHIT expression in cutaneous squamous cell carcinomas.

Aberrations of the tumor suppressor gene, the fragile histidine triad gene (FHIT), have been reported in a wide variety of human cancers including cervical carcinoma, oral squamous cell carcinoma (SCC) and oesophageal SCC. This study aimed to examine the integrity of the FHIT gene in cutaneous SCC. Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 21 histologically confirmed cutaneous SCC at two microsatellite markers, D3S1300 and D3S4103, both of which are located within intron 5 of the FHIT gene. Immunohistochemical analysis of FHIT protein expression was also examined in the cutaneous SCC. Ten of the 16 informative cutaneous SCC samples (63%) displayed AI/LOH at the D3S1300 locus, and 13 of the 17 informative cutaneous SCC samples (76%) displayed AI/LOH at the D3S4103 locus. Nine of the 21 SCC samples were found to be positive for FHIT protein expression, however, a further nine SCC samples showed reduced FHIT expression, and three SCC samples did not express the FHIT protein. No correlation between AI/LOH of the FHIT gene and reduced/absent FHIT expression was detected in the cutaneous SCC samples. Further investigation into the role of the FHIT protein in the epidermis is warranted to determine if the reduced/lost expression of FHIT observed in a subset of the cutaneous SCC is contributing to tumorigenesis.

Molecular genetic analysis of the BRCA2 tumor suppressor gene region in cutaneous squamous cell carcinomas.

BACKGROUND: Germ line mutations of the BRCA2 tumor suppressor gene with subsequent loss of the remaining wild-type BRCA2 allele have been identified in up to 35% of familial breast cancer cases. A high frequency of allelic loss at the BRCA2 gene locus has also been reported in a variety of sporadic epithelial tumors including oesophageal squamous cell carcinomas (SCC), and sporadic head and neck SCC. AIM: The present study aimed to examine the integrity of the BRCA2 gene in cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 22 histologically confirmed cutaneous SCC at two microsatellite markers, D13S260 (centromeric to the BRCA2 gene) and D13S267 (telomeric to the BRCA2 gene). Immunohistochemical analysis of BRCA2 protein expression was also examined in the cutaneous SCC. RESULTS: AI/LOH at the D13S260 locus was found in eight of the 19 informative SCC, and AI/LOH at the D13S267 locus was found in 12 of the 18 informative SCC. Seven SCC showed allelic loss at both markers, and six SCC showed retention of heterozygosity at both markers. Expression of BRCA2 protein was only detected in six of the normal epidermises and three of the 21 SCC examined. CONCLUSION: AI/LOH of the BRCA2 gene region was found to be common in the cutaneous SCC.

Enhanced detection of microsatellite instability and mismatch repair gene expression in cutaneous squamous cell carcinomas.

BACKGROUND: Microsatellite instability (MSI) is a phenotypic characteristic of tumors with biallelic inactivation of mismatch repair genes, such as MSH2 or MLH1, and contributes to malignant transformation. AIMS: The aim of this study was to examine the prevalence of MSI in cutaneous squamous cell carcinoma (SCC) using a PCR and fluorescent-based detection system. These methods of analysis offer several advantages over the use of silver staining and autoradiographic techniques. We also aimed to determine if MSI status correlated with expression of the MSH2 and MLH1 mismatch repair proteins in these cutaneous SCC samples. METHODS: The MSI status of 22 histologically confirmed invasive cutaneous SCC samples were analyzed at five microsatellite markers (the National Cancer Institute's Bethesda panel of two mononucleotide and three dinucleotide markers) using a PCR and fluorescent-based detection system. Immunohistochemical analysis of MSH2 and MLH1 protein expression was also carried out on the SCC samples. RESULTS: Only one case of cutaneous SCC displayed MSI. This was found at just one of five markers, and thus was low frequency MSI. All 22 cutaneous SCC cases strongly expressed MSH2 protein. Eighteen (82%) of the cutaneous SCC cases showed moderate to strong expression of MLH1 protein. The remaining four cases of cutaneous SCC were negative for MLH1 protein. Therefore, the majority of the SCC patients analyzed showed a correlation between absence of MSI and expression of MSH2 and MLH1 proteins. CONCLUSIONS: MSI is uncommon in cutaneous SCC. In addition, MSH2 was strongly expressed in all SCC samples analyzed and appeared to be upregulated when compared with the corresponding normal tissue. MLH1 protein was not detected in 4 of 22 SCC cases, although it was expressed in the corresponding normal tissue, suggesting that inactivation of MLH1 may be a late event in a subset of invasive SCC cases.

Analysis of p16 expression and allelic imbalance / loss of heterozygosity of 9p21 in cutaneous squamous cell carcinomas.

Deletions of the short arm of chromosome 9 have been reported in different types of malignancies. This chromosomal region contains a number of known tumour suppressor genes, including the p16INK4A (CDKN2A), p15INK4B and MTAP tumour suppressor genes located at 9p21. In this study twenty-two paraffin embedded invasive cutaneous SCC were examined for allelic imbalance/ loss of heterozygosity (AI/LOH) of the 9p region (in particular 9p21), and for p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells and analysed for AI/LOH by using six fluorescently labelled microsatellite markers that map to the 9p region. P16 protein expression was examined by immunohistochemistry. At each of the six microsatellite markers the majority of SCC analysed showed AI/LOH. Overall both AI/LOH within the CDKN2A locus and absence of p16 protein expression were frequent among the cutaneous SCC analysed, suggesting that p16 inactivation may play a role in cutaneous SCC development. The majority of the SCC analysed also had AI/LOH of the marker within the MTAP gene, and at markers flanking the CDKN2A gene; thus further investigation as to a possible role for these genes in the development of cutaneous SCC is warranted.