Regional impact assessment of air quality improvement: The air quality lifecourse assessment tool (AQ-LAT) for the West Midlands combined authority (WMCA).

Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, ∼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months. The 2021 Environment Act established a legal framework for local authorities in England to develop regional air quality plans, generating a policy need for predictive environmental impact assessment tools. In this context, we developed a novel Air Quality Lifecourse Assessment Tool (AQ-LAT) to estimate electoral ward-level impacts of PM2.5 and NO2 exposure on outcomes of interest to local authorities, namely morbidity (asthma, coronary heart disease (CHD), stroke, lung cancer), mortality, and associated healthcare costs. We apply the Tool to assess the health economic burden of air pollutant exposure and estimate benefits that would be generated by meeting WHO 2021 Global Air Quality Guidelines (AQGs) (annual average concentrations) for NO2 (10 µg/m3) and PM2.5 (5 µg/m3) in the West Midlands Combined Authority Area. All West Midlands residents live in areas which exceed WHO AQGs, with 2070 deaths, 2070 asthma diagnoses, 770 CHD diagnoses, 170 lung cancers and 650 strokes attributable to air pollution exposure annually. Reducing PM2.5 and NO2 concentrations to WHO AQGs would save 10,700 lives reducing regional mortality by 1.8%, gaining 92,000 quality-adjusted life years (QALYs), and preventing 20,500 asthma, 7400 CHD, 1400 lung cancer, and 5700 stroke diagnoses, with economic benefits of £3.2 billion over 20 years. Significantly, we estimate 30% of QALY gains relate to reduced disease burden. The AQ-LAT has major potential to be replicated across local authorities in England and applied to inform regional investment decisions.

Temporary Urbanisms as Policy Alternatives to Enhance Health and Well-Being in the Post-Pandemic City.

PURPOSE OF REVIEW: While there has been extensive discussion on the various forms of temporary uses in urban settings, little is known on the ways in which temporary and health urbanisms connect. Now, a turning point has been reached regarding the interactions between health and the built environment and the contributions made by urban planning and other built environment disciplines. In the context of the post-pandemic city, there is a need to develop a health-led temporary urbanism agenda than can be implemented in various settings both in the Global South and North. RECENT FINDINGS: Health-led temporary urbanism requires a reinterrogation of current models of urban development including designing multifunctional spaces in urban environments that provide sites for temporary urbanism-related activities. A healthy city is an adaptable city and one that provides opportunities for citizen-led interventions intended to enhance well-being by blending the temporary with the permanent and the planned with the improvised. Health-led temporary urbanism contributes to the call for more trans- and inter-disciplinary discussions allowing to more thoroughly link urban planning and development with health.

COVID-19 and Alternative Conceptualisations of Value and Risk in GPN Research.

The COVID-19 pandemic represents a major disturbance that has rippled across the world's population, states, economy, and central nervous system or global production networks transforming the traditional roles of states, firms, individuals/consumers, and geographies of production. This paper offers a critical and context-based approach to understanding globalization and localization by challenging the conceptualization of 'value' and 'risk' within the current global production networks framework as well as identifying key operational strategies in risk management and national security. An analysis of the adaptation strategies of the GPNs of 91 companies identifies the role played by four different forms of value in configuring production networks. This is to balance 'economic value' with non-price-based sources of value and alternative values. The analysis underscores the critical role of the state in ensuring national and human security as well as its increasing power as a key actor in GPNs and the global economy.

COVID-19, Virtual Church Services and a New Temporary Geography of Home.

The COVID-19 pandemic and subsequent lockdown measures implemented by the United Kingdom government from 23 March 2020 led to unprecedented adaptations from individuals and communities including places of worship, their clergy and congregations. This paper through a multi-disciplinary dialogue between human geography and theology explores the interrelations between place, space and the spiritual. It identifies the bricolage mechanisms that were developed rapidly by churches to shift towards providing virtual church services. This was an uncommon practice by Christian denominations in the UK. COVID-19 changed the rules requiring new practices to emerge resulting in a new form of infrasecular space to emerge. Such rapid transformations through the provision of online services and virtual embeddedness blurred the lines between sacred and secular spaces. During virtual services, the minister's home is temporally linked to the homes of congregants forming an intersacred space. Homes and spaces within homes are transformed into temporary sacred spaces.

Factors associated with discharge disposition on an acute palliative care unit.

PURPOSE: Acute palliative care units (APCUs) admit patients with cancer for symptom control, transition to community palliative care units or hospice (CPCU/H), or end-of-life care. Prognostication early in the course of admission is crucial for decision-making. We retrospectively evaluated factors associated with patients' discharge disposition on an APCU in a cancer center. METHODS: We evaluated demographic, administrative, and clinical data for all patients admitted to the APCU in 2015. Clinical data included cancer diagnosis, delirium screening, and Edmonton Symptom Assessment System (ESAS) symptoms. An ESAS sub-score composed of fatigue, drowsiness, shortness of breath, and appetite (FDSA) was also investigated. Factors associated with patients' discharge disposition (home, CPCU/H, died on APCU) were identified using three-level multinomial logistic regression. RESULTS: Among 280 patients, the median age was 65.5 and median length of stay was 10 days; 155 (55.4%) were admitted for symptom control, 65 (23.2%) for transition to CPCU/H, and 60 (21.4%) for terminal care. Discharge dispositions were as follows: 156 (55.7%) died, 63 (22.5%) returned home, and 61 (21.8%) were transferred to CPCU/H. On multivariable analysis, patients who died were less likely to be older (OR 0.97, p = 0.01), or to be admitted for symptom control (OR 0.06, p < 0.0001), and more likely to have a higher FDSA score 21-40 (OR 3.02, p = 0.004). Patients discharged to CPCU/H were less likely to have been admitted for symptom control (OR 0.06, p < 0.0001). CONCLUSION: Age, reason for admission, and the FDSA symptom cluster on admission are variables that can inform clinicians about probable discharge disposition on an APCU.

Patient-Reported Functional Status in Outpatients With Advanced Cancer: Correlation With Physician-Reported Scores and Survival.

CONTEXT: Performance status measures are increasingly completed by patients in outpatient cancer settings, but are not well validated for this use. OBJECTIVES: We assessed performance of a patient-reported functional status measure (PRFS, based on the Eastern Cooperative Oncology Group [ECOG]), compared with the physician-completed ECOG, in terms of agreement in ratings and prediction of survival. METHODS: Patients and physicians independently completed five-point PRFS (lay version of ECOG) and ECOG measures on first consultation at an oncology palliative care clinic. We assessed agreement between PRFS and ECOG using weighted Kappa statistics, and used linear regression to determine factors associated with the difference between PRFS and ECOG ratings. We used the Kaplan-Meier method to estimate the patients' median survival, categorized by PRFS and ECOG, and assessed predictive accuracy of these measures using the C-statistic. RESULTS: For the 949 patients, there was moderate agreement between PRFS and ECOG (weighted Kappa 0.32; 95% CI: 0.28-0.36). On average, patients' ratings of performance status were worse by 0.31 points (95% CI: 0.25-0.37, P < 0.0001); this tendency was greater for younger patients (P = 0.002) and those with worse symptoms (P < 0.0001). Both PRFS and ECOG scores correlated well with overall survival; the C-statistic was higher for the average of PRFS and ECOG scores (0.619) than when reported individually (0.596 and 0.604, respectively). CONCLUSION: Patients tend to rate their performance status worse than physicians, particularly if they are younger or have greater symptom burden. Prognostic ability of performance status could be improved by using the average of patients and physician scores.

Metallothionein-I/II Promotes Axonal Regeneration in the Central Nervous System.

The adult CNS does not spontaneously regenerate after injury, due in large part to myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo-A, and oligodendrocyte-myelin glycoprotein. All three inhibitors can interact with either the Nogo receptor complex or paired immunoglobulin-like receptor B. A conditioning lesion of the sciatic nerve allows the central processes of dorsal root ganglion (DRG) neurons to spontaneously regenerate in vivo after a dorsal column lesion. After a conditioning lesion, DRG neurons are no longer inhibited by myelin, and this effect is cyclic AMP (cAMP)- and transcription-dependent. Using a microarray analysis, we identified several genes that are up-regulated both in adult DRGs after a conditioning lesion and in DRG neurons treated with cAMP analogues. One gene that was up-regulated under both conditions is metallothionein (MT)-I. We show here that treatment with two closely related isoforms of MT (MT-I/II) can overcome the inhibitory effects of both myelin and MAG for cortical, hippocampal, and DRG neurons. Intrathecal delivery of MT-I/II to adult DRGs also promotes neurite outgrowth in the presence of MAG. Adult DRGs from MT-I/II-deficient mice extend significantly shorter processes on MAG compared with wild-type DRG neurons, and regeneration of dorsal column axons does not occur after a conditioning lesion in MT-I/II-deficient mice. Furthermore, a single intravitreal injection of MT-I/II after optic nerve crush promotes axonal regeneration. Mechanistically, MT-I/II ability to overcome MAG-mediated inhibition is transcription-dependent, and MT-I/II can block the proteolytic activity of α-secretase and the activation of PKC and Rho in response to soluble MAG.

The oncology palliative care clinic at the Princess Margaret Cancer Centre: an early intervention model for patients with advanced cancer.

Several recently published randomized controlled trials have demonstrated the benefits of early palliative care involvement for patients with advanced cancer. In the oncology outpatient setting, palliative care clinics are an ideal site for the provision of early, collaborative support, which can be maintained throughout the cancer trajectory. Despite this, access to ambulatory palliative care clinics is limited, even at tertiary cancer centres. Existing programs for outpatient palliative care are variable in scope and are not well described in the literature. We describe the development and expansion of an outpatient palliative care clinic at the Princess Margaret Cancer Centre, Toronto, Canada, demonstrating how the clinic functions at a local and regional level. This clinic served as the intervention for a recent large cluster-randomized trial of early palliative care. The model for this service can be adapted by other palliative care programs that aim to provide early, integrated oncology care.

Modified Edmonton Symptom Assessment System including constipation and sleep: validation in outpatients with cancer.

CONTEXT: The Edmonton Symptom Assessment System (ESAS) measures the severity of nine symptoms. Constipation and sleep disturbance are common in patients with cancer, but are not currently included in the ESAS. OBJECTIVES: To validate the numerical rating scale (NRS) versions of ESAS and its revised version (ESAS-r), with the additional symptoms of constipation and sleep (CS), and to assess patient preference for either version. METHODS: Outpatients with advanced cancer (N = 202) completed three assessments during a single clinic visit: ESAS-CS, and an added time window of "past 24 hours"; ESAS-r-CS, with a time window of "now" and symptom definitions; and the Memorial Symptom Assessment Scale (MSAS). Internal consistency was calculated using Cronbach's alpha. Paired t-tests compared ESAS-CS and ESAS-r-CS scores; these were correlated with MSAS using Spearman correlation coefficients. Test-retest reliability at 24 hours was assessed in 26 patients. RESULTS: ESAS-CS and ESAS-r-CS total scores correlated well with total MSAS (Spearman's rho 0.62 and 0.64, respectively). Correlation of individual symptoms with MSAS symptoms ranged from 0.54-0.80 for ESAS-CS and 0.52-0.74 for ESAS-r-CS. Although participants preferred the ESAS-r-CS format (42.8% vs. 18.6%) because of greater clarity and understandability, the "past 24 hours" time window (52.8%) was favored over "now" (21.3%). Shortness of breath and nausea correlated better for the "past 24 hours" time window (0.8 and 0.72 vs. 0.74 and 0.64 in ESAS-r-CS, respectively). The 24-hour test-retest of the ESAS-CS demonstrated acceptable reliability (intraclass correlation coefficient = 0.69). CONCLUSION: The ESAS-CS and ESAS-r-CS NRS versions are valid and reliable for measuring symptoms in this population of outpatients with advanced cancer. Although the ESAS-r-CS was preferred, patients favored the 24-hour time window of the ESAS-CS, which also may best characterize fluctuating symptoms.

Simple prognostic model for patients with advanced cancer based on performance status.

PURPOSE: Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. METHODS: ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. RESULTS: Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C-statistic was similar for all three scales and ranged from 0.63 to 0.64. CONCLUSION: We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models.

Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.

Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease.

Addition of methadone to another opioid in the management of moderate to severe cancer pain: a case series.

BACKGROUND: Previous research has reported improved pain after adding methadone to another opioid, but did not quantify this benefit using a validated outcome measure. OBJECTIVE: To assess quantitatively the effectiveness of adding methadone to another opioid for moderate to severe cancer-related pain. DESIGN: All outpatients attending the Oncology Palliative Care Clinic from September 2010-September 2011, who had received methadone, were identified from pharmacy records. Inclusion criteria included: histological diagnosis of malignancy, age >18 years, taking regular opioids and Edmonton Symptom Assessment System (ESAS) pain score ≥ 4. MEASUREMENT: The primary outcome measure was a decrease in pain score of ≥ 2 points from methadone initiation to one-month follow-up (or closest available ESAS). RESULTS: Twenty patients were available for analysis, 16 of whom had neuropathic pain (80%). Eight patients (40%) had a decrease in pain score of ≥ 2 points at 1 month and a further 7 (35%) had a decrease of ≥ 2 points at the closest available time point. The mean pain score decreased from 7.7 +/- 1.8 to 5.2 +/- 2.4 from time of initiation to time of evaluation. The mean daily routine morphine equivalent, (excluding methadone), was 338 +/- 217.8 mg/day at initiation and 332 +/- 191 mg/day at evaluation; for methadone, mean doses at initiation and evaluation were 4.4 +/- 1.4 mg/day and 15.5 +/- 5.9 mg/day, respectively. Methadone was well tolerated in 17 patients (85%). CONCLUSIONS: The addition of methadone was associated with improved pain control for patients with moderate to severe pain on another opioid and appears to offer a safe, well-tolerated and practical alternative in this situation.

Impact of an oncology palliative care clinic on access to home care services.

Home care (HC) is important for patients with cancer as performance status declines. Our study of 1224 patients at a Canadian cancer center examined the impact of an oncology palliative care clinic (OPCC) on HC referral. The HC referral frequency was calculated before and after the first OPCC consultation, in total and according to performance status (Palliative Performance Scale, PPS). Characteristics associated with HC referral were investigated. After the first OPCC consultation, there was an increase in HC referral from 39% (477 of 1224; 49% of those with PPS ≤60) to 69% (841 of 1224; 88% of those with PPS ≤60). Factors independently associated with HC referral were poor PPS (P < .001) and older age (P = .003). Thus OPCC involvement resulted in markedly increased HC referrals, particularly for older patients with poor performance status.

Working with evaluation stakeholders: A rationale, step-wise approach and toolkit.

In the broad field of evaluation, the importance of stakeholders is often acknowledged and different categories of stakeholders are identified. Far less frequent is careful attention to analysis of stakeholders' interests, needs, concerns, power, priorities, and perspectives and subsequent application of that knowledge to the design of evaluations. This article is meant to help readers understand and apply stakeholder identification and analysis techniques in the design of credible evaluations that enhance primary intended use by primary intended users. While presented using a utilization-focused-evaluation (UFE) lens, the techniques are not UFE-dependent. The article presents a range of the most relevant techniques to identify and analyze evaluation stakeholders. The techniques are arranged according to their ability to inform the process of developing and implementing an evaluation design and of making use of the evaluation's findings.

Interconversion of three measures of performance status: an empirical analysis.

PURPOSE: To construct empirically a conversion table to convert performance status scores among the Eastern Cooperative Oncology Group (ECOG), Karnofsky Performance Status (KPS) and Palliative Performance Scale (PPS) measures, using a large sample of patients with advanced cancer. METHODS: Seven physicians completed assessments on 1385 consecutive patients attending an oncology palliative care clinic, or admitted to an acute cancer palliative care unit. The three measures were distributed as a questionnaire package; the order in which they were presented was randomly assigned for each week. Scales were compared using the hit rate and the weighted kappa coefficient (κ(w)). The KPS and PPS were compared directly; for comparisons of either scale with the ECOG, all 70 possible categorisations of KPS and PPS were computed. An 'ideal' categorisation was selected based on maximisation of both statistical methods. RESULTS: The KPS and PPS matched in 1209 out of 1385 assessments (hit rate 87%; κ(w) 0.97). For both the KPS and the PPS, the categorisation of 100 (ECOG 0), 80-90 (1), 60-70 (2), 40-50 (3), 10-30 (4) had the highest hit rate (75%), and the second highest κ(w) (0.84, p<0.0001). One other combination had a slightly higher κ(w) (0.85 for both KPS and PPS), but a lower hit rate (73% for KPS, 72% for PPS). CONCLUSIONS: We have derived empirically a conversion scale among the ECOG, KPS and PPS scales. The proposed scale provides a means of translating amongst these measures, which may improve accuracy of communication about performance status amongst oncology clinicians and researchers.

Administrative outcomes five years after opening an acute palliative care unit at a comprehensive cancer center.

PURPOSE: We examined administrative outcomes after opening an oncology acute palliative care unit (APCU), to determine attainment of administrative targets related to the unit's function of acute palliation. METHODS: We retrospectively reviewed the administrative database for our APCU for the 5 years following its opening in 2003. Data were abstracted on demographic information, as well as source of admission, primary reason for admission, discharge destination, inpatient death rate, and length of stay. Linear regression and the Cochran-Armitage trend test were used for analysis. In keeping with targets set at the unit's opening, our primary hypotheses were that outpatient admissions, admissions for symptom control, and discharges home would increase over the study period; secondary hypotheses were that length of stay and inpatient death rate would decrease. RESULTS: There were 1748 admissions during the study period: the median age was 64, 54% were women, and the most common cancer sites were gastrointestinal (24%), lung (20%), and gynecologic (13%). There were significant changes for all primary endpoints: outpatient admissions increased from 47% to 70% (p < 0.0001), admissions for symptom control increased from 42% to 75% (p < 0.0001), and discharges home increased from 18% to 39% (p < 0.0001). The secondary end points of death rate and length of stay decreased from 65% to 40% (p < 0.0001) and 12 to 11 days (p = 0.54), respectively. CONCLUSION: Setting and adhering to administrative targets for an APCU is possible with appropriate admission criteria, adequate community resources, and education of patients, families and health professionals regarding the model of care.

Predictors of symptom severity and response in patients with metastatic cancer.

We examined determinants of symptom severity and response to treatment among 150 patients with cancer participating in a phase II trial of a palliative care team intervention. Patients completed a modified Edmonton Symptom Assessment Scale (ESAS) at baseline and 1 week. Women had a worse baseline ESAS Distress Score (EDS; P = .003) and Total Distress Score (TDS; P = .005); differences were particularly marked for anxiety and appetite. Performance status was inversely associated with EDS, TDS, well-being, appetite, and fatigue (Kruskal-Wallis, all P < .005). Multivariate analysis of covariance (ANCOVA) showed that symptom improvement was independently predicted by worse baseline EDS score and female gender. Performance status, gender, and baseline symptom severity should be accounted for in trials of palliative care interventions; inclusion criteria based on symptom severity should also be considered.

Nurse and physician inter-rater agreement of three performance status measures in palliative care outpatients.

INTRODUCTION: Performance status (PS) scales are used widely in oncology practice and research. We compared inter-rater agreement, between nurses and physicians, for three commonly used PS scales. MATERIALS AND METHODS: Patients attending an oncology palliative care clinic were assessed by a physician and nurse who blindly completed Eastern Cooperative Oncology Group (ECOG), Karnofsky PS (KPS), and palliative PS (PPS) scales. Patients completed the Edmonton symptom assessment system (ESAS). RESULTS: Inter-rater agreement (weighted kappa) for the 457 patients was 0.67 for the ECOG, 0.74 for the KPS, and 0.72 for the PPS. There was no difference between proportions of physicians' vs. nurses' ratings of KPS, >60 vs.

Phase II study of an outpatient palliative care intervention in patients with metastatic cancer.

PURPOSE: Although there is increasing advocacy for timely symptom control in patients with cancer, few studies have assessed outpatient palliative care clinics. This study assessed prospectively the efficacy of an Oncology Palliative Care Clinic (OPCC) in improving patient symptom distress and satisfaction. PATIENTS AND METHODS: Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests. RESULTS: Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P < or = .005) and 1 month (all P < or = .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month. CONCLUSION: This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.