Application of constructivism and cognitive flexibility theory to build a Comprehensive, Integrated, Multimodal Interprofessional Education and Practice (CIM-IPEP) program.

Interprofessional Education (IPE) is challenging to implement and assess due to barriers preventing interprofessional communication, inadequately defined accreditation criteria, ambiguous professional roles and responsibilities, and the inherently "ill-structured" educational construct of IPE. To address these gaps, a novel comprehensive, integrated, and multimodal interprofessional education and practice (CIM-IPEP) curriculum involving students from pharmacy, medicine, psychology, and nursing professional degree programmes was created. CIM-IPEP was carefully designed based on cognitive flexibility theory (CFT) to reinforce the complexities associated with teaching and learning for multi-faceted and dynamic domains such as IPE. CFT emphasises pluralistic representation, repetition, and cognitive layering in experiential learning for ill-structured domains. Thus, CIM-IPEP was vertically and horizontally aligned within individual colleges and included diverse IPE experiences in required courses such as Foundations of IPE, and high-fidelity simulation events, culminating in an IPE-Hotspotting elective, which exposed learners to real-world patient cases. Cases were presented in a format of increasing complexity emphasising the integration of foundational and skills-based learning using constructivist methods such as Team-Based and Case-Based Learning. CIM-IPEP offers a novel IPE model. Here we present a stepwise development and implementation blueprint for similar IPE programmes that is readily transferable to other health profession education (HPE) programmes.

CCAR1, a key regulator of mediator complex recruitment to nuclear receptor transcription complexes.

DNA-bound transcription factors recruit many coactivator proteins to remodel chromatin and activate transcription. The Mediator complex is believed to recruit RNA polymerase II to most protein-encoding genes. It is generally assumed that interaction of Mediator subunits with DNA-binding transcription factors is responsible for Mediator recruitment to promoters. However, we report here that Mediator recruitment by nuclear receptors (NR) requires a coactivator protein, CCAR1 (cell-cycle and apoptosis regulator 1). CCAR1 associates with components of the Mediator and p160 coactivator complexes and is recruited to endogenous NR target genes in response to the appropriate hormone. Reduction of endogenous CCAR1 levels inhibited hormone-induced expression of endogenous NR target genes, hormone-induced recruitment of Mediator components and RNA polymerase II to target gene promoters, and estrogen-dependent growth of breast cancer cells. Thus, CCAR1 regulates expression of key proliferation-inducing genes. CCAR1 also functions as a p53 coactivator, suggesting a broader role in transcriptional regulation.

Readmission After Resections of the Colon and Rectum: Predictors of a Costly and Common Outcome.

BACKGROUND: Readmission rates are a measure of surgical quality and an object of clinical and regulatory scrutiny. Despite increasing efforts to improve quality and contain cost, 6% to 25% of patients are readmitted after colorectal surgery. OBJECTIVE: The aim of this study is to define the predictors and costs of readmission following colorectal surgery. DESIGN: This is a retrospective cohort study of patients undergoing elective and nonelective colectomy and/or proctectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007 to 2011. Readmission is defined as inpatient admission within 30 days of discharge. Univariate analyses were performed of sex, age, Elixhauser score, race, insurance type, procedure, indication, readmission diagnosis, cost, and length of stay. Multivariate analysis was performed by logistic regression. Sensitivity analysis of nonemergent admissions was conducted. SETTINGS: This study was conducted in Florida acute-care hospitals. PATIENTS: Patients undergoing colectomy and proctectomy from 2007 to 2011 were included. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The primary outcomes measured were readmission and the cost of readmission. RESULTS: A total of 93,913 patients underwent colectomy; 14.7% were readmitted within 30 days. From 2007 to 2011, readmission rates remained stable (14.6%-14.2%, trend p = 0.1585). After multivariate adjustment, patient factors associated with readmission included nonwhite race, age <65, and a diagnosis code other than neoplasm or diverticular disease (p < 0.0001). Patients with Medicare or Medicaid were more likely to be readmitted than those with private insurance (p < 0.0001). Patients with longer index admissions, those with stomas, and those undergoing all procedures other than sigmoid or transverse colectomy were more likely to be readmitted (p < 0.0001). High-volume hospitals had higher rates of readmission (p < 0.0001). The most common reason for readmission was infection (32.9%). Median cost of readmission care was $7030 (intraquartile range, $4220-$13,247). Fistulas caused the most costly readmissions ($15,174; intraquartile range, $6725-$26,660). LIMITATIONS: Administrative data and retrospective design were limitations of this study. CONCLUSIONS: Readmissions rates after colorectal surgery remain common and costly. Nonprivate insurance, IBD, and high hospital volume are significantly associated with readmission.

Review of thalidomide use in the pediatric population.

Thalidomide is resurging in the management of adult rheumatologic skin conditions, especially lupus erythematosus. Although use in pediatric patients is reported since the 1990s, there are no systematic reviews describing treatment in children. Thalidomide has immunomodulatory and anti-tumor necrosis factor-α effects as well as antiangiogenic properties, making it useful for a broad spectrum of inflammatory disorders. Thalidomide is second-line treatment for aphthous stomatitis and chronic graft-versus-host disease in children and has been prescribed for many other conditions including actinic prurigo and epidermolysis bullosa pruriginosa. Systemic lupus erythematosus may be less responsive to thalidomide in children than adults. Peripheral neuropathy is observed in both idiosyncratic and dose-dependent relationships; children older than 12 years may be more susceptible to developing this adverse effect than younger patients. There are rare reports of thrombotic complications in children treated for nonmalignant indications. We review the mechanism of action and propose that thalidomide is an alternative treatment for patients who fail or have contraindications to anti-tumor necrosis factor-α biologics.

Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6ß4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder.

Appendicitis in the modern era: universal problem and variable treatment.

BACKGROUND: Acute appendicitis is the second most common gastrointestinal diagnosis mandating urgent operation in the U.S. The current state of adult appendectomy, including patient and hospital characteristics, complications, and predictors for complications, are unknown. METHODS: Retrospective review of U.S. Nationwide Inpatient Sample 2003-2011 for appendectomy in ≥18-year-olds was performed. Primary outcomes measures included postoperative complications, length of stay, and patient mortality. Categorical variables were analyzed by χ2, trend analyses by Cochran-Armitage. Multivariable logistic regression was performed to adjust for predictors of developing complications. RESULTS: 1,663,238 weighted appendectomy discharges occurred. Over the study period, complications increased from 3.2 to 3.8% (p < 0.0001), but the overall mortality decreased from 0.14 to 0.09% (p < 0.0001) and mean LOS decreased from 3.1 to 2.6 days (p < 0.0001). The proportion of laparoscopic appendectomy increased over time, 41.7-80.1% (p < 0.0001). Patients were increasingly older (≥65 years: 9.4-11.6%, p < 0.0001), more obese (3.8-8.9%, p < 0.0001), and with more comorbidities (Elixhauser score ≥3: 4.7-9.8%, p < 0.0001). After adjustment, independent predictors for postoperative complications included: open surgery (OR 1.5, 95% C.I. 1.4-1.5), male sex (OR 1.6, 95% CI 1.5-1.6), black race (vs. white: OR 1.5, 95% CI 1.4-1.6), perforated appendix (OR 2.8, 95% CI 2.7-3.0), greater comorbidity (Elixhauser ≥3 vs. 0, OR 11.3, 95% CI 10.5-12.1), non-private insurance status (vs. private: Medicaid OR 1.3, 95% CI 1.2-1.4; Medicare OR 1.7, 95% CI 1.6-1.8), increasing age (>52 years vs. ≤27: OR 1.3; 95% CI 1.2-1.4), and hospital volume (vs. high: low OR 1.2; 95% CI 1.1-1.3). Predictors of laparoscopic appendectomy were age, ethnicity, insurance status, comorbidities, and hospital location. CONCLUSIONS: Laparoscopic appendectomy is increasing but is unevenly deployed across patient groups. Appendectomy patients were increasingly older, with more comorbidities and with increasing rates of obesity. Black patients and patients with public insurance had less utilization of laparoscopy and inferior outcomes.

Surgical management of chronic pancreatitis: current utilization in the United States.

BACKGROUND: Surgical intervention is uncommon in chronic pancreatitis. Literature largely describes single institution or international experiences. This study describes US-based chronic pancreatitis surgical management. METHODS: Retrospective analysis of chronic pancreatitis patients in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007-2011. Patients with malignancy or congenital abnormalities were excluded. Univariate analysis using the chi-square test. The number of readmissions, inpatient length of stay and cost using Wilcoxon's signed-rank test. Multivariate analysis of surgery by logistic regression. RESULTS: Twenty-one thousand four hundred and forty-five patients with chronic pancreatitis. 10.8% (2 307) underwent surgery including 1652 cholecystectomies, 564 drainage procedures and 498 pancreatectomies. Procedures decreased from 12.1% to 8.3% over time (P < 0.001), but intervention within 3 months increased (7.2% to 8.4%; P = 0.017). 15.3% (3 278) had pancreatic cysts/pseudocysts and 43.4% (9 312) had diabetes. The median numbers of admissions were 2 [interquartile range (IQR) 1,5] and 3 (IQR 2,7) among non-surgical and surgical patients, respectively (P < 0.001). Predictors of surgery were fewer co-morbidities, private insurance, and either diabetes mellitus or pancreatic cyst/pseudocyst. CONCLUSION: Chronic pancreatitis leads to numerous inpatient readmissions, but surgical intervention only occurs in a minority of cases. Complicated patients are more likely to undergo surgery. The complexities of chronic pancreatitis management warrant early multidisciplinary evaluation and ongoing consideration of surgical and non-surgical options.

Outcomes in operative management of pancreatic cancer.

Pancreatic cancer is a highly lethal malignancy that often presents at an advanced stage. Surgical resection can prolong survival and offers the only potential for cure. However, pancreatectomy is associated with significant morbidity and mortality. This article reviews perioperative outcomes, post-resection long-term survival, and innovations in the surgical management of pancreatic cancer.

Structure-based drug design of diphenyl α-aminoalkylphosphonates as prostate-specific antigen antagonists.

Here, we describe the mechanism of diphenyl α-aminoalkylphosphonate ester derivatives as potent inhibitors of prostate-specific antigen (PSA), a likely protease responsible for the advancement of prostate tumor progression. The AutoDock 4.2 molecular docking suite was utilized to model covalent and noncovalent binding of this class of inhibitors to predict crystallographic poses and compare experimental IC50 dose-response curves and in silico potencies for providing future more specific rational drug design. The new lead compound R/S-diphenyl[N-benzyloxycarbonylamino(4-carbamoylphenyl)methyl]phosphonate is being reported in this study as a potent inhibitor of PSA activity (IC50 = 250 nM; AutoDock Score = -8.29/-9.14 kJ·mol(-1) for R/S). Molecular dynamics (MD) simulations using GROMACS 4.6.5 was used to obtain trajectories of the top ligand and validate key interactions in the binding complex. A hydrogen-bonding map was used to confirm interactions between the lead compound and residues THR190, SER217, and SER227 in the P1 pocket. The modeling study introduces novel aminoalkylphosphonates as a potential drug candidate for targeting PSA by optimizing P1 binding affinities.

Highly stable polyaniline-poly(sodium 4-styrenesulfonate) nanoparticles for sensing of amines.

Sensing technology is the key of intelligent packaging. A variety of different sensing systems for indicating freshness through intelligent packaging have been presented. Polyaniline (PANI) can change its color reversibly through the acid-base reaction with reactive compounds and has been widely used in different kinds of sensors. However, because PANI is insoluble in common organic solvents, this limits its practical usage in many applications. In this work, a highly stable polyaniline-poly(sodium 4-styrenesulfonate) (PANI:PSS) colloid has been developed as a facile colorimetric sensor of volatile amines. The results showed the PANI:PSS colloid is quite sensitive to changes in pH. When PANI:PSS colloids were homogenously deposited on filter paper, the paper are used as a sensor to detect triethylamine (TEA) vapor. The green color of the test paper changed to blue at a TEA concentration as low as 188 ppm.

Congenital kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon successfully treated with low-dose radiation therapy.

Kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon is a life-threatening vasculopathy. The current mainstay treatment for KHEs is corticosteroids and chemotherapy, but these medications do not work for all patients and carry significant side effects. We report a neonate with a large congenital KHE who responded extremely well to low-dose radiation therapy.

Patient selection and the volume effect in pancreatic surgery: unequal benefits?

BACKGROUND: The volume effect in pancreatic surgery is well established. Regionalization to high-volume centres has been proposed. The effect of this proposal on practice patterns is unknown. METHODS: Retrospective review of pancreatectomy patients in the Nationwide Inpatient Sample 2004-2011. Inpatient mortality and complication rates were calculated. Patients were stratified by annual centre pancreatic resection volume (low <5, medium 5-18, high >18). Multivariable regression model evaluated predictors of resection at a high-volume centre. RESULTS: In total, 129,609 patients underwent a pancreatectomy. The crude inpatient mortality rate was 4.3%. 36.0% experienced complications. 66.5% underwent a resection at high-volume centres. In 2004, low-, medium- and high-volume centres resected 16.3%, 24.5% and 59.2% of patients, compared with 7.6%, 19.3% and 73.1% in 2011. High-volume centres had lower mortality (P < 0.001), fewer complications (P < 0.001) and a shorter median length of stay (P < 0.001). Patients at non-high-volume centres had more comorbidities (P = 0.001), lower rates of private insurance (P < 0.001) and more non-elective admissions (P < 0.001). DISCUSSION: In spite of a shift to high-volume hospitals, a substantial cohort still receives a resection outside of these centres. Patients receiving non-high-volume care demonstrate less favourable comorbidities, insurance and urgency of operation. The implications are twofold: already disadvantaged patients may not benefit from the high-volume effect; and patients predisposed to do well may contribute to observed superior outcomes at high-volume centres.

Exploring the Complexities of Long COVID.

Since the emergence of the SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 million deaths have been reported globally. Despite most individuals recovering within four weeks, the Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such as age, gender, comorbidities, initial COVID-19 severity, and vaccine interactions, and delves into potential mechanisms, including immune responses, viral persistence, and gut dysbiosis. Moreover, we conclude that women, advanced age, comorbidities, non-vaccination, and low socioeconomic status all appear to be risk factors. The reasons for these differences are still not fully understood and likely involve a complex relationship between social, genetic, hormonal, and other factors. Furthermore, individuals with Long COVID-19 seem more likely to endure economic hardship due to persistent symptoms. In summary, our findings further illustrate the multifaceted nature of Long COVID and underscore the importance of understanding the epidemiological factors and potential mechanisms needed to develop effective therapeutic strategies and interventions.

Epidermodysplasia verruciformis-associated eccrine neoplasm: a rare entity with distinctive clinical and histopathologic features.

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology. Clinical follow-up for one patient has been benign to date. These tumors show strong similarity to two previously reported cases, suggesting that this type of EDV-associated eccrine neoplasia may represent a rare but reproducible form of skin adnexal tumor with distinctive clinicopathologic features.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Frequency-potency analysis of IgG+ memory B cells delineates neutralizing antibody responses at single-cell resolution.

Identifying individual functional B cell receptors (BCRs) is common, but two-dimensional analysis of B cell frequency versus BCR potency would delineate both quantity and quality of antigen-specific memory B cells. We efficiently determine quantitative BCR neutralizing activities using a single-cell-derived antibody supernatant analysis (SCAN) workflow and develop a frequency-potency algorithm to estimate B cell frequencies at various neutralizing activity or binding affinity cutoffs. In an HIV-1 fusion peptide (FP) immunization study, frequency-potency curves elucidate the quantity and quality of FP-specific immunoglobulin G (IgG)+ memory B cells for different animals, time points, and antibody lineages at single-cell resolution. The BCR neutralizing activities are mainly determined by their affinities to soluble envelope trimer. Frequency analysis definitively demonstrates dominant neutralizing antibody lineages. These findings establish SCAN and frequency-potency analyses as promising approaches for general B cell analysis and monoclonal antibody (mAb) discovery. They also provide specific rationales for HIV-1 FP-directed vaccine optimization.

Strategies Used by Healthcare Systems to Communicate with Hospitalized Patients and Families with Limited English Proficiency During the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic disproportionately affected racial and ethnic minorities in the United States, including many with limited English proficiency (LEP). These patients face various communication barriers, including a shortage of available interpreters and the need for masks that exacerbated communication barriers. It is not known how hospitals responded to these unique challenges to providing language services for the large number of patients with LEP during COVID-19. This narrative review assessed literature and lay media to identify strategies utilized by hospitals to communicate with patients with LEP hospitalized during the COVID-19 pandemic. A search of APA PsychInfo, EBM Reviews, Embase, Ovid MEDLINE, Epub Ahead of Print, and Ebsco Megafile initially yielded 61 articles, 6 of which were ultimately included after reviewing abstracts and full texts. The identified interventions, which sought to increase accessibility of language-concordant care, increase accessibility of professional interpretation, and improve family communication and understanding, were described positively, though only one was tested for effectiveness.

Pacific patients' reasons for attending the emergency department of Counties Manukau for non-urgent conditions.

AIM: To determine Pacific patients' reasons for Emergency Department (ED) use for non-urgent conditions by Pacific people at Counties Manukau Health. METHODS: Patients who self-presented to Counties Manukau ED with a non-urgent condition in June 2019 were surveyed. Responses to open-ended questions were analysed using a general inductive approach, in discussion with key stakeholders. RESULTS: Of 353 participants with ethnicity reported, 139 (39%) were Pacific, 66 (19%) Maori and 148 (42%) were non-Maori non-Pacific, nMnP. A total of 58 (42%) of Pacific participants had been to their general practitioner prior to presenting to the ED; this proportion was similar for Maori (19 [30%]) and nMnP (59 [40%]) (p=0.215). The most common reasons for ED attendance among Pacific (as well as other) participants were 1) advice by a health professional (41%, 95% CI 33-50%), 2) usual care unavailable (28%, 20-36%), 3) symptoms not improving (21%, 14-28%), and 4) symptoms too severe to be managed elsewhere (19%, 12-26%). CONCLUSIONS: Multiple reasons underlie non-urgent use of EDs by Pacific and other ethnic groups. These reasons need to be considered simultaneously in the design, implementation, and evaluation of multi-dimensional initiatives that discourage non-urgent use of EDs to ensure that such initiatives are effective, equitable, and unintended consequences are avoided.