Planning for faecal sludge management in informal urban settlements of low-income countries :a study of Lusaka, Republic of Zambia

PhD ThesisFaecal Sludge Management is regarded as an affordable and viable option for providing sanitation services in complex informal urban settlements. This thesis examines to what extent current urban sanitation planning approaches and practices are suitable frameworks for achieving sustainable Faecal Sludge Management in informal settlements. The findings are based on a mixed methodology approach where primary data was collected from household level questionnaires (N=169) and a series of key informant interviews (N=35 at city and country level, N=14 at community level) during 2013 in Lusaka, Zambia. The development of a decision support tool that allows for the modelling, costing and comparison of various Faecal Sludge Management infrastructure and technology scenarios was also completed. The findings conclude that whilst many urban sanitation planning approaches exist, adaptation is required so that sustainable Faecal Sludge Management systems can be achieved in complex informal environments. Firstly, a more in depth understanding of social structures, dominant influences and their effect on service provision is required. In particular, an understanding of the role of politics, power, trust and history was shown to be vital. Insights from various decision-making domains including household, community, city and country level representatives was shown to be essential. Application of the developed decision support tool highlighted that obtaining accurate spatio-topological information on the existing sanitation and transport infrastructure networks and on the status and capacity of the containment, removal and transportation components of the Sanitation Value Chain is critical. These are required to ensure accurate long-term cost projections can be developed for various modelled scenarios, that comparisons can be made against other sanitation technologies and where appropriate, sustainable services can be implemented. This research bridges a gap in the sanitation sector by highlighting key socio-technical factors that need to be addressed in order to achieve sustainable sanitation provision for informal settlements in Zambia and beyond

Is the sanitation sector ready for the post 2015 goals? Lessons learnt from Zambia

The new post 2015 targets and indicators for sanitation pose a new challenge for the sector. Developing countries will have to achieve sanitation service provision which goes beyond access to a toilet and ensures the adequate management of excreta beyond the containment facility. To establish whether the sector is ready for such a challenge, this paper looks to draw upon research findings from informal settlements in Lusaka, Zambia. The presentation will define factors which should be addressed that may directly impact on the achievement of the post 2015 indicators and how successfully they can be monitored

Network modelling for road-based fecal sludge management

Improvements in the collection and treatment of sewage are critical to reduce health and environmental hazards in rapidly urbanising informal settlements. Where sewerage infrastructure is not available, road-based faecal sludge management options are often the only alternative. However, the costs of faecal sludge transportation are often a barrier to its implementation and operation and thus it is desirable to optimise travel time from source to treatment to reduce costs. This paper presents a novel technique, employing spatial network analysis, to optimise the spatiotopological configuration of a road-based faecal sludge transportation network on the basis of travel time. Using crowd-sourced spatial data for the Kibera settlement and the surrounding city, Nairobi, a proof-of-concept network model was created simulating the transport of waste from the 158 public toilets within Kibera. The toilets are serviced by vacuum pump trucks which move faecal sludge to a transfer station, and from there a tanker transports waste to a treatment plant. The model was used to evaluate the efficiency of different network configurations, based on transportation time. The results show that the location of the transfer station is a critical factor in network optimisation, demonstrating the utility of network analysis as part of the sanitation planning process

A novel, high-rate, anaerobic digester to treat high-solids waste ensuring reuse and good sanitation planning

A consortium of UK universities is working on developing a novel anaerobic digester that will treat pit latrine waste and transform it into a safe and valuable product. Physico-chemical characteristics of fresh human waste and pit latrine sludge are being determined. This is informing the development of a bioreactor containing biofilms, or slimes, of several microbial ‘trophic’ groups growing preferentially on distinct surfaces and materials. The ecologically-engineered bioreactor design will optimise the efficiency of the treatment and underpin successful digestion of high-solids waste. The potential use of the digestate will be reused in agriculture to recycle nutrients and prevent environmental, and watercourse pollution. Attitudes to sanitation, as well as to resource recovery from, and reuse of, waste, are being investigated so the participatory sanitation planning process can work effectively

Network modelling for road-based Faecal Sludge Management

Improvements in the collection and treatment of sewage are critical to reduce health and environmental hazards in rapidly-urbanising informal settlements. Where sewerage infrastructure is not available, road-based Fecal Sludge Management options are often the only alternative. However, the costs of fecal sludge transportation are often a barrier to their implementation and operation and thus it is desirable to optimise travel time from source to treatment to reduce costs. This paper presents a novel technique, employing spatial network analysis, to optimise the spatio-topological configuration of a road-based fecal sludge transportation network on the basis of travel time. Using crowd-sourced spatial data for the Kibera settlement and the surrounding city, Nairobi, a proof-of-concept network model was created simulating the transport of waste from the 158 public toilets within Kibera. The toilets are serviced by vacuum pump trucks which move fecal sludge to a transfer station from where a tanker transports waste to a treatment plant. The model was used to evaluate the efficiency of different network configurations, based on transportation time. The results show that the location of the transfer station is a critical factor in network optimisation, demonstrating the utility of network analysis as part of the sanitation planning process

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients