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

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

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Resurrecting inactive antimicrobial peptide from LPS trap : activity, LPS-interactions and conformations of a hybrid peptide of temporin B and beta-boomerang motif.

Antimicrobial peptides are short defensive peptides that represent a promising therapeutic option to eradicate antimicrobial resistant strains that has long since been increasing in number. Temporin B is a natural antimicrobial peptide that has shown reduced efficacy on Gram-negative strains due to its tendency to oligomerize on the lipopolysaccharide feature of the outer membrane. Conjugating Temporin B to a synthetic lipopolysaccharide binding motif termed β-boomerang domain, formed a synthetic peptide, LG21, with vastly improved antimicrobial activity. In this study, we attempt to understand the role of Temporin B component of LG21 by truncating the Temporin B portion, forming synthetic peptide LG14. LG14 was shown to have reduced antimicrobial activity but was still able to permeate the bacterial outer membrane and inner membrane, though comparatively less efficient in the latter. Fluorescence assays highlighted limited discrimination between eukaryotic membrane mimic and bacterial inner membrane mimic. Structural elucidation by circular dichroism and nuclear magnetic resonance spectroscopy of LG14 were in agreement on an α-helical conformation at bound state. NMR also indicated that the α-helix has little amphipathicity. Collectively, these results demonstrate that Temporin B played a role in conferring LG21 with antimicrobial activity especially in recognition and perturbation of the bacterial inner membrane.Bachelor of Science in Biological Science

Sonic Knowledge Production in Archaeoacoustics: Echoes of elsewhere?

This thesis is a critical investigation into the production of knowledge in archaeoacoustics. The recently emerged field of acoustic archaeology explores how sound and listening might relate to human behaviour as evidenced in material remains from the past. Pursuing a methodology of sounding situated knowledges and tracing the figure of the echo as a material-semiotic actor, this research project asks to what extent sonic knowledge production in archaeoacoustics challenges the visually-dominant epistemology of Eurocentric thought. In the first in-depth analysis of how sonic knowledge is produced in the field to date, this thesis uses interviews of researchers as well as participant-observer fieldwork at the caves of Isturitz-Oxocelhaya and Arcy-sur-Cure, France as well as at Chavín de Huántar, Peru to describe the formation of archaeoacoustics as a discipline. Archaeoacoustics uses sound to conceive of an alterity, often to imply that past cultures were more sound-oriented. I diagnose prevalent trends of sonic knowledge production in archaeoacoustics as sonic positivism and sonic naturalism. I take the capacity of a sonic alterity to task by asking what kind of political-philosophical “elsewhere” is being imagined. I argue that despite the ontoepistemological potential of sound evident in archaeoacoustics, sonic knowledge production in the field has been unable to fully respond to the challenge that the sonic makes to visuocentric Western conceptions of knowledge. Echoes have been important to archaeoacoustics, yet remain bound to Eurocentric conceptualisations. In response to these current limitations, the thesis reconceptualises echo as a feminist and decolonial sonic figuration. In introducing a theory of aural gnosis to address alternative modalities of knowing through sound and listening, my thesis explores whether echoes can indicate an “elsewhere” of possibilities for the notion of knowledge itself

Morbidity And Mortality in Patients After Skull Base Osteomyelitis. A Report of 3 Cases and Review of the Literature. (.pdf)

Skull base osteomyelitis (SBO) is an uncommon but life threatening condition, most commonly secondary to otitis externa (1). We report 3 cases of SBO which presented with neuro-ophthalmic manifestations without aural pathology. Knowledge of SBO by the neuro-ophthalmologist is essential

Multi-level determinants of breast cancer screening among Malay-Muslim women in Singapore: a sequential mixed-methods study

10.1186/s12905-022-01972-yBMC WOMENS HEALTH22

"It Will Lead You to Make Better Decisions about Your Health"-A Focus Group and Survey Study on Women's Attitudes towards Risk-Based Breast Cancer Screening and Personalised Risk Assessments

10.3390/curroncol29120719CURRENT ONCOLOGY29129181-919

BREAst screening Tailored for HEr (BREATHE)-A study protocol on personalised risk-based breast cancer screening programme

10.1371/journal.pone.0265965PLOS ONE17