Longitudinal clusters of pain and stiffness in polymyalgia rheumatica: 2-year results from the PMR Cohort study

Objectives. To investigate potential subgroups of primary care diagnosed patients with polymyalgia rheumatica (PMR) based on self-reported pain and stiffness severity over time.Methods. 652 people with an incident PMR diagnosis were recruited from English general practices and completed a baseline postal questionnaire. They were followed-up with a further six questionnaires over a two-year period. 446 people completed 2-year follow-up. Pain and stiffness were reported on 0-10 numerical rating scales. Latent class growth analysis was used to estimate the joint trajectories of pain and stiffness overtime. A combination ofstatistical and clinical considerations was used to choose the number of clusters. Characteristics of the classes were described. Results. Five clusters were identified. One cluster represented the profile of ‘classical’ PMR symptoms and one represented sustained symptoms that may not be PMR. The other three clusters displayed a partial recovery, a recovery followed by worsening and a slow, but sustained recovery. Those displaying classical PMR symptoms were in better overall health at diagnosis than the other groups.Conclusions. PMR is a heterogeneous condition, with a number of phenotypes. The spectrum of presentation, as well as varying responses to treatment, may be related to underlying health status at diagnosis. Future research should seek to stratify patients at diagnosis to identify those likely to have a poor recovery and in need of an alternative treatment pathway. Clinicians should be aware of the different experiences of patients and monitor symptoms closely, even where there is initial improvement

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

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

He kete hauora taiao: A Bicultural Ecological Assessment Framework

Ka mau tonu ngā taonga tapu o ngā matua tupuna Koinei ngā taonga i tuku iho, na te ātua Hold fast to the treasures of the ancestors For they are the treasures that have been handed down to us by God’ (Dymond, 2013, p. 274) Ecologists, resource managers, landowners and iwi generally strive to manage biodiversity on their whenua as obliged by legislation. This may include restoration, protection, the mitigation of negative human impacts, or the prevention of further habitat loss. Mainstream ecological science and resource management (ERM) usually guides management decisions and provides evidence of management effectiveness. However, ecological science can struggle with stochastic and complex biological systems. Māori have hundreds of years of environmental knowledge and understanding that could be utilised by mainstream resource managers to enhance society's combined knowledge. An assessment tool that places mātauranga at its core can introduce a Māori perspective, privilege Māori knowledge, enable holistic co-management, re/introduce social values and create a common ground on which the two paradigms can connect. He Kete Hauora Taiao is an environmental assessment framework for terrestrial habitats constructed on Māori ecological health indicators by applying them to quantitative ecological scientific data. He Kete Hauora Taiao is built on the Driver – Pressure – State/Condition – Indicator – Response framework (K. F. D. Hughey, Cullen, Kerr, & Cook, 2004). Māori ecological perspectives or ariā (indicators, perspectives or concepts) are placed at the ‘condition’ level. Ariā include concepts such as mauri, whakapapa, tapu, wairua and mahinga kai which are linked to environmental structures, processes, functions and services. These ecological indicators can then be assessed with recognised qualitative scientific tools, metrics and targets. ESAT, Ecological State Assessment Tool, is a database that accompanies He Kete Hauora Taiao and enables quantitative ecological data to be viewed through a Māori perspective and weighted according to its relevance to management objectives. Creating a new bicultural environmental assessment framework required the exploration of the intersection between Māori ecological knowledge (MEK) and ERM. To my knowledge this is the first MEK based ecological assessment framework created specifically for terrestrial habitats and the first one to attempt to quantify MEK ecological indicators, relate them to ecology and resource management metrics and develop an interface between the two epistemologies. He Kete Hauora Taiao and ESAT (Ecological Statement Assessment Tool) are valuable resource management tools. Together they can create resource management programmes informed by a Māori value framework and are tailored to specific whenua, iwi agendas and political reporting and management requirements. He Kete Hauora Taiao spans the intersection between ERM and MEK, enabling communication and translation. MEK may provide context to scientific data and the scientific data may help augment understanding of MEK. Combined, MEK and ERM may create a powerful force that could vastly improve our resource management and conservation efforts. He Kete Hauora Taiao is a framework that could be engaged with by territorial authorities, iwi kaitiaki and landowners nationwide to automatically build te ao Māori into our management practices

The urban release of captive-reared Kaka at Karori Wildlife Sanctuary : a thesis presented in partial fulfillment of the requirements of the degree of Master of Science in Ecology at Massey University, Palmerston North

study investigates the first reintroduction of captive-reared Kaka (Nestor meridionalis), an endangered parrot endemic to New Zealand, at Karori Wildlife Sanctuary, a predator free privately run sanctuary in the same vein as the Department of Conservation's mainland islands. Three Kaka from Auckland Zoo and three Kaka from Hamilton Zoo were released into Karori Sanctuary in August 2002 and followed until August 2003. The Kaka were fitted with radio transmitters, and coloured bands before release. Before release, the consumption of supplementary foods was monitored and the Kaka were introduced to natural foods. The Kaka showed no significant temporal trends, and no correlation between the two groups. The Kaka showed marked preferences for some foods and very varied consumption of others. The Kaka instinctively foraged on natural foods that were provided. Provisioning of natural foods may have reduced neo-phobic responses and assisted successful transition to the wild. Five of the six Kaka remained at the sanctuary 13 Months after release. The Hamilton Kaka tended to disperse further than the Auckland Kaka. All the Hamilton Kaka left the valley where as non of the Auckland birds did. RP-P left the valley and few to Island Bay eventually to return, RR-P went west to beyond Makara peak, and RW-P is the only Kaka to leave and not return. An un-banded wild male arrived at the sanctuary in January 2002 and has reminded since. RP-P and P-WY nested in December 2003 and 3 chicks fledged in March 2003, the pair nested again in 2004 along with RR-P and P-WB. The largest part of the Kaka activity budget is foraging. Supplementary food is a large part of the Kaka diet and the more time a bird spent foraging on natural foods the less time they spent at the feeder. The Kaka at Karori developed a unique location call, and there was evidence of this being taught to the Auckland Kaka by the Hamilton Kaka. Use of the feeder was taught to the wild Kaka that arrived and to the chicks. These results suggest that captive-reared Kaka adapt well to release and supports Berry's (1998) findings. Captive-reared Kaka showed an ability to forage effectively on natural foods, had a high level of site fidelity, and formed stable population. Using captive-reared Kaka is an effective management tool, and the presence of an urban environment did not reduce the success of the release