Peri-operative management and analgesic strategy for a patient undergoing quadruple limb amputation.

Inadequately managed amputation pain can contribute to postoperative morbidity and mortality. However, amputation pain can be challenging to manage due to its complex nature, with both central and peripheral nociceptive and neuropathic elements. Here, we present the case of a 47-year old man who developed irreversible ischaemic injuries to all four limbs following admission to intensive care with sepsis. He required quadruple amputation and we describe our approach to his peri-operative management including anaesthesia, invasive monitoring and the multi-modal approach to his peri-operative management using a combination of intravenous analgesics, bilateral brachial plexus nerve catheters and a combined spinal and epidural. The patient made a good recovery and was able to return home from a rehabilitation facility 12 months after the operation, able to undertake many tasks himself with the aid of prosthetics.

Real-world multiple myeloma risk factors and outcomes by non-Hispanic Black/African American and non-Hispanic White race/ethnicity in the United States.

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the United States. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White patients at diagnosis (median 68 vs 71 years) and more likely to be female (53.4% vs 43.5%). Rates of high-risk cytogenetics and 1q21+ were similar between races/ethnicities. The most common primary regimen used was lenalidomide-bortezomib-dexamethasone (50.1% of NH Black/AA and 48.1% of NH White patients). Receipt of stem cell transplantation during first LOT was less common among NH Black/AA (16.5%) than NH White (21.9%) patients. Unadjusted RW progression-free survival (rwPFS) and overall survival (rwOS) were similar between races/ethnicities. After multivariable adjustment, NH Black/AA race/ethnicity was associated with slightly inferior rwPFS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27). The difference in rwOS (HR 1.12; 95% CI 0.98-1.28) was not statistically significant. In general, associations between risk factors for rwPFS and rwOS were consistent between races/ethnicities. Findings from this analysis help to inform clinicians about the impact of race/ethnicity on MM treatment paradigms and outcomes in the United States.

Treatment of Relapsed B/T-cell Mixed Phenotype Acute Leukemia With Blinatumomab.

Here, we describe the treatment of a patient with relapsed/refractory B/T mixed phenotype acute leukemia (MPAL) using blinatumomab monotherapy, the first bispecific T cell engager (BiTE) approved by the FDA for relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). A 64-year-old man with a history of stage 3 chronic kidney disease and type 2 diabetes mellitus was discovered to have B/T MPAL on bone marrow biopsy during hospitalization for dyspnea due to pulmonary embolism. The patient achieved brief remission with blinatumomab treatment before succumbing to neutropenic sepsis. The lack of sufficient data to guide therapy in MPAL remains a challenge, highlighting the potential of new targeted approaches such as blinatumomab to improve outcomes in relapsed/refractory MPAL.

Patients and Families' Participation in Multidisciplinary Tumor Conferences Improves Patient and Family-Focused Cancer Care: Lessons Learned From a Debate on the Role of Radiation Therapy in Primary Mediastinal Non-Hodgkin Lymphoma.

Incorporation of patients' preferences often leads to improved outcomes when included in the multidisciplinary tumor conference/board (MTC). However, patients' wishes are not included or considered in the MTC decision-making. We need better strategies and approaches for patient-inclusive, shared decision-making. When finding ourselves at a crossroads regarding the next step in a patient's treatment, we saw a unique opportunity for an MTC with the patient and her husband in attendance. The results of a full literature review regarding the role of consolidative radiation therapy (RT) in a patient with primary (thymic) B-cell lymphoma after completion of chemotherapy and fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) scan with a Deauville score of 4 were presented in a creative, engaging debate-style forum with visual aids. The patient and her husband were able to follow the discussion and, in the end, a consensus recommendation, heavily focused on the patient's preferences, was offered and adopted, which ultimately resulted in the avoidance of excess treatment and likely improved her long-term quality of life outcome. These collaborative and innovative interactions benefit not only our patients but enrich our lives too as healthcare providers and strengthen us as a cancer care team in terms of understanding diversity in decision-making processes.

Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

An assessment of introducers used for airway management.

Different introducers are available to assist with tracheal intubation. Subtle differences in the design of introducers can have a marked effect on safety and performance. The Difficult Airway Society's Airway Device Evaluation Project Team proposal states that devices should only be purchased for which there is at least a case-control study on patients assessing airway devices. However, resources are not currently available to carry out a case-control study on all introducers available on the market. This study comprised a laboratory and manikin-based investigation to identify introducers that could be suitable for clinical investigation. We included six different introducers in laboratory-based assessments (design characteristics) and manikin-based assessments involving the participation of 30 anaesthetists. Each anaesthetist attempted placement in the manikin's trachea with each of the six introducers in a random order. Outcomes included first-time insertion success rate; insertion success rate; number of attempts; time to placement; and distance placed. Each anaesthetist also completed a questionnaire. First-time insertion success rate depended significantly on the introducer used (p = 0.0016) and varied from 47% (Armstrong and P3) to 77% (Intersurgical and Frova). Median time to placement (including oesophageal placement) varied from 10 s (Eschmann and Frova) to 20 s (P3) (p = 0.0025). Median time to successful placement in the trachea varied from 9 s (Frova) to 22 s (Armstrong) (p = 0.037). We found that the Armstrong and P3 devices were not as acceptable as other introducers and, without significant improvements to their design and characteristics, the use of these devices in studies on patients is questionable. The study protocol is suitable for differentiating between different introducers and could be used as a basis for assessing other types of devices.

A demonstration of using formal consensus methods within guideline development; a case study.

BACKGROUND: Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these. METHODS: We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations. RESULTS: The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance. CONCLUSION: Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

Surfactant-Free One-Pot Synthesis of Homogeneous Trimetallic PtNiCu Nanoparticles with Size Control by Using Glycine.

Homogeneous platinum alloy nanoparticles (NPs) are of great interest to the electrocatalytic community for potential use in various fuel cell electrodes. Increasing the surface area available per unit mass by decreasing the size of NPs while maintaining or improving activity is one of the key tasks of fuel cell catalysis. Achieving both in a synthesis of multielement NPs is still a challenging workup. In this investigation, we report the use of glycine as a size control agent to make ultrasmall homogeneous trimetallic PtNiCu NPs within 2-5 nm range. The mechanistic roles of dimethyl formamide (DMF), formaldehyde, water, and glycine are explored to understand the formation of these small NPs. Interestingly, it was observed that these PtNiCu NPs exhibited substantially enhanced mass activities toward the electro-oxidation of ethanol in comparison to commercial Pt black.

Management of mesh complications following surgery for stress urinary incontinence or pelvic organ prolapse: a systematic review.

BACKGROUND: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications. OBJECTIVE: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'. SEARCH STRATEGY: Search strategies were developed for each indication for referral. SELECTION CRITERIA: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen. DATA COLLECTION AND ANALYSIS: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. MAIN RESULTS: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. CONCLUSIONS: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future. TWEETABLE ABSTRACT: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.

The composition and stability of the faecal microbiota of Merino sheep.

AIMS: To determine the composition and temporal stability of the gut (faecal) microbiota of sheep (Ovis aries). METHODS AND RESULTS: Microbial population dynamics was conducted using ARISA (28 sheep) and 16S rRNA sequencing (11 sheep). Firmicutes and Bacteroidetes were the predominant bacterial phyla, constituting ~80% of the total population. The core faecal bacterial microbiota of sheep consisted of 67 of 136 detected families and 91 of 215 detected species. Predominant microbial taxa included Ruminococcaceae, unassigned families in Bacteroidales and Clostridiales, Verrucomicrobiaceae and Paraprevotellaceae. Diversity indices and core microbiota composition demonstrated the stability of the core microbiota over 2-4 weeks. The core microbiota remained similar over ~5 months. CONCLUSIONS: Temporal stability of the sheep microbiota is high over 2-4 weeks in the absence of experimental variables. The core microbiota of Merino sheep shares taxa found in other breeds of sheep and other ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous studies seek to investigate the impact of experimental variables on gut microbiota composition. To do so, knowledge of the innate stability (or instability) of the microbiota over an experimental time course is required, independent of other variables. We have demonstrated high stability of the gut microbiota in sheep over 3-4 weeks, with moderate stability over ~5 months.

Primary surgical management of anterior pelvic organ prolapse: a systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP. METHODS: We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective. MAIN RESULTS: We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values. CONCLUSIONS: Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty. TWEETABLE ABSTRACT: New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse.

Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

Development of a Model of Hemispheric Hypodensity ("Big Black Brain").

Subdural hematoma (SDH) is the most common finding after abusive head trauma (AHT). Hemispheric hypodensity (HH) is a radiological indicator of severe brain damage that encompasses multiple vascular territories, and may develop in the hemisphere(s) underlying the SDH. In some instances where the SDH is predominantly unilateral, the widespread damage is unilateral underlying the SDH. To date, no animal model has successfully replicated this pattern of injury. We combined escalating severities of the injuries and insults commonly associated with HH including SDH, impact, mass effect, seizures, apnea, and hypoventilation to create an experimental model of HH in piglets aged 1 week (comparable to human infants) to 1 month (comparable to human toddlers). Unilateral HH evolved over 24 h when kainic acid was applied ipsilateral to the SDH to induce seizures. Pathological examination revealed a hypoxic-ischemic injury-type pattern with vasogenic edema through much of the cortical ribbon with relative sparing of deep gray matter. The percentage of the hemisphere that was damaged was greater on the ipsilateral versus contralateral side and was positively correlated with SDH area and estimated seizure duration. Further studies are needed to parse out the pathophysiology of this injury and to determine if multiple injuries and insults act synergistically to induce a metabolic mismatch or if the mechanism of trauma induces severe seizures that drive this distinctive pattern of injury.

Development and performance of a biomimetic artificial perilymph for in vitro testing of medical devices.

OBJECTIVE: Cochlear implants interface with the fluid in the cochlea called perilymph. The volume of this fluid present in human and animal model cochlea is prohibitively low for isolation for in vitro studies. Thus, there is a need for an artificial perilymph that reflects the complexity of this fluid in terms of competitive protein adsorption. APPROACH: This study established a biomimetic artificial perilymph (BAP) comprising serum albumin, immunoglobulin G, transferrin, inter-alpha-trypsin inhibitor, apolipoprotein A1 and complement C3 to represent the major components of human perilymph. Adsorption of the BAP components to platinum was analysed. MAIN RESULTS: It was established that this six component BAP provided competitive and complex adsorption behaviours consistent with biologically derived complex fluids. Additionally, adsorption of the BAP components to platinum cochlear electrodes resulted in a change in polarisation impedance consistent with that observed for the cochlear device in vivo. SIGNIFICANCE: This study established a BAP fluid suitable for furthering the understanding of the implant environment for electroactive devices that interface with the biological environment.

Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer.

BACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer. METHODS: Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria. RESULTS: Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies. CONCLUSION: The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.

Engineered cysteine antibodies: an improved antibody-drug conjugate platform with a novel mechanism of drug-linker stability.

Antibody-drug conjugates (ADCs) are fulfilling the promise of targeted therapy with meaningful clinical success. An intense research effort is directed towards improving pharmacokinetic profiles, toxicity and chemical stability of ADCs. The majority of ADCs use amide and thioether chemistry to link potent cytotoxic agents to antibodies via endogenous lysine and cysteine residues. While maleimide-cysteine conjugation is used for many clinical stage ADC programs, maleimides have been shown to exhibit some degree of post-conjugation instability. Previous research with site-directed mutagenic incorporation of cysteine residues for conjugation revealed that the stability of the drug-antibody linkage depends on the site of conjugation. Here we report on a collection of engineered cysteine antibodies (S239C, E269C, K326C and A327C) that can be site-specifically conjugated to potent cytotoxic agents to produce homogenous 2-loaded ADCs. These ADCs confirm that site of conjugation impacts maleimide stability and present a novel mechanism of thioether stabilization, effectively unlinking stability from either local chemical environment or calculated solvent accessibility and expanding the current paradigm for ADC drug-linker stability. These ADCs show potent in vitro and in vivo activity while delivering half of the molar equivalent dose of drug per antibody when compared to an average 4-loaded ADC. In addition, our lead engineered site shields highly hydrophobic drugs, enabling conjugation, formulation and clinical use of otherwise intractable chemotypes.

The impact of neighbourhood walkability on the effectiveness of a structured education programme to increase objectively measured walking.

Background: Incorporating physical activity into daily activities is key for the effectiveness of lifestyle education interventions aimed at improving health outcomes; however, consideration of the environmental context in which individuals live is not always made. Walkability is a characteristic of the physical environment, and may be a potential facilitator to changing physical activity levels. Methods: Using data collected during the Walking Away from Diabetes randomized controlled trial, we examined the association between the walkability of the home neighbourhood and physical activity of participants. We also determined whether home neighbourhood walkability of participants was associated with the intervention effect of the education programme. Results: Data from 706 participants were available for analysis. Neighbourhood walkability was not significantly associated with any of the physical activity measures at baseline, or at 12, 24 or 36 months following the intervention (P > 0.05 for all). There was no association between walkability and change in purposeful steps/day from baseline to 36 months in the usual care or intervention arm; 25.77 (-99.04, 150.58) and 42.97 (-327.63, 413.45), respectively. Conclusion: Neighbourhood walkability appeared to have no association with objectively measured physical activity in this population. Furthermore, the walkability of participant's neighbourhood did not influence the effectiveness of a lifestyle programme.