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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]

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]

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]

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]

The influence of smoke-derived or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and can lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune-mediator responses of human bronchoalveolar lavage cells (BALCs) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALCs containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL)-10 production. PM-loaded BALCs retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis ( M.tb ) ΔleuDΔpanCD at equal efficacy as clear non-PM-loaded BALCs. However, immune responsiveness, such as the production of IL-6 ( P = 0.015) and tumor necrosis factor-α (TNF)-α ( P = 0.0172) immediately post M. bovis BCG infection, were dramatically lower in black BALCs loaded with PM versus clear non-PM-loaded BALCs. By 24 h post infection, differential immune responses to M. bovis BCG between black versus clear BALC waned, and instead, production of IL-6 ( P = 0.03) and IL-1α ( P = 0.04) by black BALCs was lower versus clear BALCs following M.tb ΔleuDΔpanCD infection. Considering that TNF-α and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALCs loaded with inhaled PM, display lower levels of antimycobacterial mediators and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.