14 research outputs found

    Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

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    Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

    On Reduced Complexity Soft-Output MIMO ML detection

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    In multiple-input multiple-output (MIMO) fading channels maximum likelihood (ML) detection is desirable to achieve high performance, but its complexity grows exponentially with the spectral efficiency. The current state of the art in MIMO detection is list decoding and lattice decoding. This paper proposes a new class of lattice detectors that combines some of the principles of both list and lattice decoding, thus resulting in an efficient parallelizable implementation and near optimal soft-ouput ML performance. The novel detector is called layered orthogonal lattice detector (LORD), because it adopts a new lattice formulation and relies on a channel orthogonalization process. It should be noted that the algorithm achieves optimal hard-output ML performance in case of two transmit antennas. For two transmit antennas max-log bit soft-output information can be generated and for greater than two antennas approximate max-log detection is achieved. Simulation results show that LORD, in MIMO system employing orthogonal frequency division multiplexing (OFDM) and bit interleaved coded modulation (BICM) is able to achieve very high signal-to-noise ratio (SNR) gains compared to practical soft-output detectors such as minimum-mean square error (MMSE), in either linear or nonlinear iterative scheme. Besides, the performance comparison with hard-output decoded algebraic space time codes shows the fundamental importance of soft-output generation capability for practical wireless applications

    A miRNA-145/TGF-β1 negative feedback loop regulates the cancer-associated fibroblast phenotype

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    The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblasts, CAF) supportive of tumour cell invasion and metastasis. Efforts to develop new treatments targeting the tumour mesenchyme are hampered by a poor understanding of the mechanisms underlying the development of CAF. Here, we examine the contribution of microRNA to the development of experimentally-derived CAF and correlate this with changes observed in CAF derived from tumours. Exposure of primary normal human fibroblasts to TGF-β1 resulted in the acquisition of a myofibroblastic CAF-like phenotype. This was associated with increased expression of miR-145, a miRNA predicted in silico to target multiple components of the TGF-β signalling pathway. miR-145 was also overexpressed in CAF derived from oral cancers. Overexpression of miR-145 blocked TGF-β1-induced myofibroblastic differentiation and reverted CAF towards a normal fibroblast phenotype. We conclude that miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.</p
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