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Background The Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial found that a group-based educational intervention to support people using strong opioids for chronic non-malignant pain helped a significant proportion of people to stop or decrease opioid use with no increase in pain-related disability. We report a linked process evaluation of the group-based intervention evaluated in comparison to a usual-care control group that received a self-help booklet and relaxation CD.Methods We interviewed 18 intervention facilitators, and 20 intervention and 20 control participants who had chronic non-malignant pain and were recruited from general (family) practices in the UK. Quantitative data included change mechanism questions on the trial questionnaires which explored motivation, expectations and self-efficacy. Fidelity was assessed by listening to a sample of audio-recorded group sessions and nurse consultations. Quantitative and qualitative data were integrated using ‘follow a thread’ and a mixed-methods matrix.Findings Four overarching themes emerged: (1) the right time to taper, (2) the backdrop of a life with chronic pain, (3) needing support and (4) the benefits of being in a group. Delivery fidelity was good, adherence (83%) and competence (79%) across a range of intervention groups. Staff delivering the intervention found three typical responses to the intervention: resistance, open to trying and feeling it was not the right time. The group experience was important to those in the intervention arm. It provided people with a forum in which to learn about the current thinking about opioid usage and its effects. It also gave them examples of how feasible or personally relevant coming off opioids might be.Conclusion The process evaluation data showed that the I-WOTCH intervention was well delivered, well received and useful for most interviewees. Being ‘the right time’ to taper and having support throughout tapering, emerged as important factors within the context of living with chronic pain.Trial registration number ISRCTN49470934.

Xenotransplantation is a promising approach to reduce organ shortage, while genetic modification of donor pigs has significantly decreased the immunogenic burden of xenotransplants, organ rejection is still a hurdle. Genetically modified pig organs are used in xenotransplantation research, and the first clinical pig‐to‐human heart transplantation was performed in 2022. However, the impact of genetic modification has not been investigated on a cellular level yet. Endothelial cells (EC) and their sugar‐rich surface known as the glycocalyx are the first barrier encountering the recipient's immune system, making them a target for rejection. We have previously shown that wild type venous but not arterial EC were protected against heparan sulfate (HS) shedding after activation with human serum or human tumor necrosis factor alpha (TNF훼). Using a 2D microfluidic system we investigated the glycocalyx dynamics of genetically modified porcine arterial and venous EC (Gal훼1,3 Gal knock‐out, transgenic for human CD46 and thrombomodulin, GTKO/hCD46/hTM) after activation with human serum or human TNF훼. Interestingly, we observed that GTKO/hCD46/hTM arterial cells, additionally to venous cells, do not shed HS. Unscathed HS on GTKO/hCD46/hTM EC correlated with reduced complement deposition, suggesting that protection against complement activation contributes to maintaining an intact glycocalyx layer on arterial EC. This protection was lost on GTKO/hCD46/hTM cells after simultaneous perfusion with human serum and human TNF훼. HS shedding on arterial cells and increased complement deposition on both arterial and venous cells was observed. These findings suggest that GTKO/hCD46/hTM EC revert to a proinflammatory phenotype in an inflammatory xenotransplantation setting, potentially favoring transplant rejection. [ABSTRACT FROM AUTHOR]

Epidemiologic data show that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from coronavirus disease-2019 (COVID-19), and there is a similar trend for poor outcomes from Mycobacterium tuberculosis (Mtb) infection after recent SARS-CoV-2. A shared dysregulation of immunity explains the dual risk posed by co-infection, but the specific mechanisms are being explored. While initial attention focused on T cell immunity, more comprehensive analyses revealed a dysfunctional innate immune response in COVID-19, characterized by reduced numbers of dendritic cells, NK cells and a redistribution of mononuclear phagocytes towards intermediate myeloid subsets. During hyper- or chronic inflammatory processes, activation signals from molecules such as growth factors and alarmins lead to the expansion of an immature population of myeloid cells called myeloiddeprived suppressor cells (MDSC). These cells enter a state of pathological activation, lose their ability to rapidly clear pathogens, and instead become broadly immunosuppressive. MDSC are enriched in the peripheral blood of patients with severe COVID-19; associated with mortality; and with higher levels of inflammatory cytokines. In TB, MDSC have been implicated in loss of control of Mtb in the granuloma and ineffective innate and T cell immunity to the pathogen. Considering that innate immune sensing serves as first line of both anti-bacterial and anti-viral defence mechanisms, we propose MDSC as a crucial mechanism for the adverse clinical trajectories of TB-COVID-19 coinfection. [ABSTRACT FROM AUTHOR]

Author(s): Jane S. Shaw [sup.1] Author Affiliations: (1) James G. Martin Center for Academic Renewal, Raleigh, NC, USA Cents and Sensibility: What Economics Can Learn from the Humanities , by [...]

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature. [ABSTRACT FROM AUTHOR]

Key Points: Question: Among patients with chronic pain, does a multicomponent intervention consisting of group meetings, education, individual support, and skill-based learning reduce opioid use and improve pain interference with daily activities compared with usual care? Findings: In this multicentered, randomized clinical trial that included 608 participants with chronic pain due to nonmalignant causes from primary care settings in the UK, at 12-month follow-up, 29% of people in the intervention group, compared with 7% in the usual care group, discontinued opioids, but there were no statistically significant differences in pain interference with daily life activities between the 2 groups at 12 months. Meaning: Among patients with chronic pain due to nonmalignant causes, a group-based educational intervention significantly reduced opioid use had no effect on perceived pain compared with usual care. Importance: Opioid use for chronic nonmalignant pain can be harmful. Objective: To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care. Design, Setting, and Participants: Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020. Intervention: Participants were randomized 1:1 to either usual care or 3-day–long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months. Main Outcomes and Measures: The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report. Results: Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (−4.1 in the intervention and −3.17 in the usual care groups; between-group difference: mean difference, −0.52 [95% CI, −1.94 to 0.89]; P =.15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P <.001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt). Conclusions and Relevance: In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities. Trial Registration: isrctn.org Identifier: ISRCTN49470934 This randomized clinical trial compares the efficacy of a multicomponent, group-based, self-management intervention vs usual care in reducing opioid use and improving pain-related disability in patients taking strong opioids to treat chronic pain from nonmalignant causes. [ABSTRACT FROM AUTHOR]

Author(s): Jane S. Shaw [sup.1] Author Affiliations: (1) James G. Martin Center for Academic Renewal, 353 E. Six Forks Road Suite 200, 27609, Raleigh, NC, USA Don't be misled by [...]

The problem facing American colleges and universities is larger than even the term "bubble" implies. A bursting bubble would force change on the more than four thousand postsecondary institutions in the United States, but something even more destructive is going to hit higher education, probably at the same time. The major sign that a bubble is about to rupture would be a decline in enrollment--one that might start slowly, but build fast. For private schools that depend heavily on tuition, and for public universities that count on rising enrollment funding from their states, decisions by potential students to stay away could spell serious financial trouble. In this article, the author examines an array of possible post-bubble solutions, and argues that for-profit institutions may actually be in the best position to survive a financial collapse. (Contains 19 footnotes.)

A pleural exudate that remains undiagnosed after a combined clinical assessment, thoracentesis, and imaging requires a pleural biopsy for a definitive diagnosis. Thoracoscopy is often the first method of choice to obtain tissue as it offers greater sensitivity and there is a perception of less risk. However, with imaging guidance, closed pleural biopsy is a safe, affordable, and effective alternative to diagnose all forms of pleural disease. Ultrasound (US) has several benefits when compared with computed tomography for image-guided biopsy, as it is widely available, can be performed bedside, and does not expose the patient to radiation. If performed in optimal conditions, a transthoracic USguided closed pleural biopsy can yield results comparable to those of thoracoscopy and a marked reduction in the complication rate versus blind biopsy. Abrams and Tru-Cut needles are the most widely used for a closed pleural biopsy. Either may be used with real-time image guidance or with a free-hand image-assisted technique to harvest up to 6 separate tissue samples. The needle choice will depend on the morphology of the lesion observed on imaging. The Tru-Cut is generally preferred for mass lesions of the pleura or pleura that is >20 mm in thickness, and the Abrams for pleural thickening of <20 mm or radiologically normal pleura. A transthoracic US may be used to detect, rule out, and prevent complications, such as bleeding, solid organ injury, or pneumothorax. The ability to perform thoracic US is a necessary skill in current respiratory practice, and US-guided closed pleural biopsy has a critical role in diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe and compare veterinary professionals' use of shared decision-making during companion animal appointments. DESIGN: Multi-practice cross-sectional study. SAMPLE: A purposive sample of 4 companion animal veterinary clinics in a group practice in Texas. PROCEDURES: A convenience sample of veterinary appointments were recorded January to March 2018 and audio-recordings were analyzed using the Observer OPTIONS instrument to assess shared decision-making. Each decision was categorized by veterinary professional involvement. RESULTS: A total of 76/85 (89%) appointments included at least 1 decision between the client and veterinary professional(s), with a total of 129 shared decisions. Decisions that involved both a veterinary technician and veterinarian scored significantly higher for elements of shared decision-making (OPTIONS = 29.5 + 8.4; n = 46), than veterinarian-only decisions (OPTIONS = 25.4 + 11.50; P = .040; n = 63), and veterinary technician-only decisions (OPTION5 = 22.5 + 7.15; P = .001; n = 20). Specific elements of shared decision-making that differed significantly based on veterinary professional involvement included educating the client about options (OPTION5 Item 3; P = .0041) and integrating the client's preference (OPTION5 Item 5; P = .0010). CLINICAL RELEVANCE: Findings suggest that clients are more involved in decision making related to their pet's health care when both the veterinary technician and veterinarian communicate with the client. Veterinary technicians' communication significantly enhanced client engagement in decision-making when working collaboratively with the veterinarian. [ABSTRACT FROM AUTHOR]

Suggests that U.S. classrooms sometimes provide a forum for distorted views of environmental problems, noting that all those involved in education, from kindergarten through the graduate level, should be concerned about such distortions. Discusses the importance of providing students with accurate information and recommends that people directly involved in environmental education at any level should look for ways to improve on this process. (SM)

Explains free-market environmentalism, demonstrating how it is integral to environmental economics. Discusses issues such as market and government failures; the "tragedy of the commons"; and how to avoid said tragedy, focusing on the role of private property rights. Provides suggestions for history, social studies, and economics teachers on introducing economics into environmental issues. (CMK)

Reviews the theories of 18th-century social scientist Thomas Malthus regarding population and his predictions of massive worldwide famine. Maintains that countries with a tradition of private property rights can sustain a dense population and food supply. Examines the relationship between low birth rate and economic prosperity. (MJP)

OBJECTIVE To assess the impact of a 15-month, in-practice communication skills intervention on client visit satisfaction. SAMPLE 4 purposely selected veterinary clinics, 9 veterinarians, and 930 appointment-specific client satisfaction surveys. PROCEDURES The study was designed as a multipractice, preintervention-postintervention study. Practice teams participated in a 15-month communication skills intervention that included interactive group workshops and one-on-one communication coaching with the entire practice. Client Satisfaction Questionnaires were completed 3 months before (mean, 55 questionnaires/veterinarian) and after (mean, 48 questionnaires/veterinarian) the intervention. The impact of the intervention and factors associated with client visit satisfaction were evaluated with mixed logistic regression. RESULTS Client satisfaction scores were dichotomized owing to extreme negative skewness. In total, 57% (284/496) of clients were completely satisfied on pretest questionnaires, and 67% (290/434) were completely satisfied on postintervention questionnaires. The odds of clients being completely satisfied were significantly higher after the communication skills intervention (OR = 1.56; P = .002). When controlling for the intervention, predictors of client visit satisfaction included appointment type (odds of being completely satisfied were significantly higher for recheck appointments than for preventative care appointments [OR = 1.71; P = .02] and health problem appointments [OR = 1.99; P = .003]) and duration of the veterinarian-client relationship (probability increased by 0.52 with each 1-year increase in relationship duration; P = .008). CLINICAL RELEVANCE Results suggested that the client-centered, skills-based communication intervention resulted in increased client visit satisfaction. Findings contribute to current evidence that client-centered communication and duration of the veterinarian-client relationship promote client satisfaction during veterinary visits. [ABSTRACT FROM AUTHOR]

Background The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a "TB score" based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. Methods Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). Results When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI],.91–.97), sensitivity of 87% (95% CI, 77–93%) and specificity of 94% (88–97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75–97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI,.83–.94), 80% sensitivity (95% CI, 76–85%) and 94% specificity (95% CI, 91–96%). Conclusions Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status. [ABSTRACT FROM AUTHOR]

Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR • Autologous breast reconstruction is increasingly preferred over implants in the setting of radiation therapy. • Use of patient-reported outcomes is endorsed. • Shape and size of reconstructed breasts can hinder radiotherapy planning. • There is a need for randomised phase III trials. [ABSTRACT FROM AUTHOR]

* Montessori, Dewey, and Capitalism: Educational Theory for a Free Market in Education By Jerry Kirkpatrick Claremont, Calif.: TLJ Books, 2008. Pp. 212. $18.95 paper. As Thomas Jefferson famously said, [...]

Patients with secondary spontaneous pneumothorax (SSP) complicated by persistent air leak (PAL) and who are poor surgical candidates have limited treatment options. This case series explored autologous blood patch pleurodesis as a possible cost-effective management option. A total of 46 episodes of SSP with PAL were included. The procedure was successful in 33 (71.7%). Of these, 17 (51.5%) resolved within 1 day. The mean duration of intercostal drainage prior to the blood patch was 22 days in the successful group. Pneumothoraces with incomplete lung re-expansion at the time of procedure were successful in 20 of 30 (66.7%). Only human immunodeficiency virus infection was associated with failure (p = 0.03). Adverse events included transient fever (n = 3) that resolved spontaneously, and empyema (n = 3) which were successfully managed with antibiotics and pigtail drainage. We conclude that a large proportion of patients with SSP complicated by PAL who are unfit for surgery may be liberated from intercostal drainage by an autologous blood patch pleurodesis, with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Argues that well-intentioned government policies, such as the Endangered Species Act, can actually cause harm to endangered species by creating disincentives to preserving the habitat for endangered species. Maintains that the use of incentives can lead to voluntary species protection. Includes instructions for an in-class teaching activity. (MJP)