Surgical wounds healing by secondary intention (SWHSI) are increasingly being treated with negative‐pressure wound therapy (NPWT) despite a lack of high‐quality research evidence regarding its clinical and cost‐effectiveness. This pilot feasibility RCT aimed to assess the methods for and feasibility of conducting a future definitive RCT of NPWT for the treatment of SWHSI.Eligible consenting adult patients receiving care at the study sites (2 acute and 1 community) and with a SWHSI appropriate for NPWT or wound dressing treatment were randomized 1 : 1 centrally to receive NPWT or usual care (no NPWT). Participants were followed up every 1–2 weeks for 3 months. Feasibility  and clinical  outcomes were assessed.A total of 248 participants were screened for eligibility; 40 (16·1 per cent) were randomized, 19 to NPWT and 21 to usual care. Twenty‐four of the 40 wounds were located on the foot. Participants received NPWT for a median of 18 (range 0–72) days. Two participants in the NPWT group never received the intervention and 14 received NPWT within 48 h of randomization. Five participants in the usual care group received NPWT during the study. Ten of the 40 wounds were deemed to have healed during the study.http://www.iscrtn.com)A full‐scale RCT to investigate the clinical and cost‐effectiveness of NPWT for SWHSI is feasible. This study identified crucial information on recruitment rates and data collection methods to consider during the design of a definitive RCT. Registration number: ISRCTN12761776 ( The UK National Health Service (NHS) undertakes a substantial number of surgical operations every year, with most involving an incisionExisting literature focuses on guidance for the management of SWHSI; however, there is little published evidence regarding SWHSI treatment (such as type and frequency of dressings used) or wound healing rates attributable to specific treatments. Systematic reviewset al., unpublished data, 2018) showed that, even after adjustment for intergroup differences, NPWT was associated with prolonged time to healing and was highly unlikely to be cost‐effective. It is estimated  that cessation of NPWT would save the NHS between €212 and €407 (£171 and £328) million per annum , have been used increasingly as treatments for SWHSI. It is claimed that NPWT, used as part of the treatment pathway, rather than to the point of healing, may have a positive effect on wound healing by removing exudate, reducing infections and increasing tissue perfusionGiven that NPWT is used widely for SWHSI within the NHS, high‐level evidence investigating its clinical and cost‐effectiveness is required urgently. Recruitment to NPWT trials can be difficultFull details of the trial protocol have been published elsewhereTable Patients receiving care for a SWHSI from Hull and East Yorkshire Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust and Leeds Community Healthcare NHS Trust were screened against eligibility criteria by the direct care team Table . PotentiEthical approval for this study was granted by Yorkshire and Humber–Leeds East Research Ethics Committee , Renasys®  and PICO® (Smith & Nephew). The choice of device and duration of the therapy were decided by the clinical care team in conjunction with the participant. Aspects of the NPWT treatment regimen, such as pressure cycles and dressing change frequency, were according to the standard practice at the time. The only stipulation made for NPWT use was that it must be clinically appropriate. When not being treated with NPWT, participants' wounds received usual care. The type of device, dressings and pressure cycles were recorded, and any changes reported at subsequent follow‐up visits.Control group participants received usual care . The type of dressing used was not stipulated for the trial as there is no evidence to suggest that any one dressing is more clinically or cost‐effective than anotherParticipant demographics, wound and surgery characteristics, and participant self‐reported questionnaires  were collected at the baseline visit. Where participants had more than one SWHSI, the largest wound was deemed the ‘reference’ wound, and data were collected for this wound during the study.After randomization, participants were followed up for a maximum of 3 months unless they withdrew consent, died or were lost to follow‐up. Clinical data were collected by research nurses on a weekly to fortnightly basis at follow‐up assessment visits. The timing of clinical follow‐up was not standardized (beyond weekly to fortnightly) to allow the feasibility of visit frequency to be assessed. Visits continued, up to a maximum of three visits, following an assessment that deemed the wound to have healed.Feasibility outcomes included: eligibility rates  and reasons for ineligibility; participation rates  and reasons for non‐participation; withdrawal rates  and the reasons for withdrawal; ability to deliver the intervention, including time between randomization and treatment; reasons for delays in start of treatment; duration of NPWT use; reasons for NPWT cessation; and treatment crossover. The need for training to deliver NPWT was assessed via a questionnaire completed by research nurses at the end of the study.The trial protocol advised that a photograph of the wound be taken at each assessment visit. Research staff were provided with brief guidance on taking these photographs, which stipulated that the entire wound should be in view and the participant identification be included in the image. The feasibility of blinded outcome assessment of healing and treatment allocation was assessed by providing blinded assessors with copies of the wound photographs and asking them to confirm whether: they deemed the wound to be healed ; and they believed they knew the participant's treatment allocation. However, in practice it was not feasible for the blinded reviewers to assess all participant wound photographs. It was therefore decided that the last photograph taken after randomization for each participant would be used in the feasibility of blinded assessment of healing. Blinding to treatment allocation was assessed using photographs taken at week 1, as the final photograph may not reflect the originally allocated treatment given that NPWT is not necessarily used to the point of wound healing.Finally, the feasibility of collecting wound pain data scored on a scale from 0 (no pain) to 10 (worst pain imaginable) using weekly text messages was assessed.The primary clinical outcome in a definitive trial would be time in days from randomization to wound healing. Healing was assessed at each follow‐up visit by the research nurse and, when observed, the date of healing was recorded.The wound area at baseline and at each follow‐up visit was calculated using ruler measurements: without adjustment (length × width); and with adjustment, by multiplying the area by π/4 (length × width × 0·785)Participants self‐completed questionnaires at baseline, 2 weeks, and 1 and 3 months after randomization. Follow‐up questionnaires were posted with a stamped addressed envelope for return to the clinical trials unit. Questionnaires included two generic health‐related quality‐of‐life (HRQoL) instruments, Short Form 12  and EQ‐5D‐3L™ , and three pain assessment instruments: a visual analogue scale (VAS) for wound pain, and a VAS for pain experienced when wound dressings were changed, both scored from 0 (no pain) to 10 (worst pain imaginable), and the nine‐item short form of the Brief Pain Inventory (BPI)Data were collected on clinical events  and adverse events (both serious and non‐serious) throughout the trial.This was explored using total mean resource use cost and mean quality‐adjusted life‐year (QALY) per trial arm.As this was a pilot trial, and the primary objective was to determine measures of feasibility and acceptability rather than to detect a treatment effect, a formal power calculation was not conducted. The study aimed to randomize approximately 50 patients in order to assess eligibility, participation and withdrawal of participants.2 or 28 cm2 or more). Wound area was found to be associated with wound healing in an earlier cohort study conducted by the trial team , in which the median wound size among patients who received NPWT was 28 cm2. The use of mixed block sizes, without stratification by site, reduced predictability of allocation.Consenting participants were assigned 1 : 1 randomly to receive either the intervention (NPWT) or usual care (no NPWT). The randomization sequence was prepared by the trial statistician (who was not involved in study recruitment) using random permuted blocks of size 4 and 6 with stratification by wound area  using the principle of modified intention‐to‐treat on an available case basis. As this was a pilot trial, analyses are mainly descriptive in nature, with summary statistics presented overall and by trial arm according to participants' original treatment allocation, where data are available.et al., unpublished data, 2018). The stratification factor (baseline wound size), in its continuous form as opposed to being dichotomized, was also used as a co‐variable in the Cox model. The effects of SWHSI history, location of SWHSI on the body, and infection at any time during follow‐up (as a time‐dependent co‐variable) were also explored by including these, in turn, in the adjusted Cox model.Time to healing was assessed using Kaplan–Meier curves and the log rank test, recognizing that the study was not powered to detect a treatment effect, and that this was not a trial objective. Cox proportional hazards regression was used to investigate the impact of co‐variables shown to be important in an earlier SWHSI cohort, including contamination level of surgery, duration of wound in days (time from surgery that resulted in SWHSI to randomization), and presence of infection at baseline (I. Chetter versus tracings) used in the study.Bland–Altman plotsRecruitment commenced at Hull and East Yorkshire Hospitals NHS Trust on 20 November 2015, at Leeds Teaching Hospitals NHS Trust on 9 February 2016, and at Leeds Community Healthcare NHS Trust on 3 March 2016, and ran for a total of 7 months, closing at all sites on 30 June 2016. Follow‐up continued for a further 3 months, until 30 September 2016.Fig. Delays in receipt of local research and development approvals were observed for two sites, owing to circumstances within the local trusts beyond the control of the research team. This affected the recruitment rate in the first 3 months of the trial; however, after the opening of all three recruitment sites, the study achieved the recruitment target (7 participants per month) in the remaining 4 months of recruitment. In total, 41 participants were randomized into the trial. One participant was subsequently found to be ineligible, as they had previously received NPWT on their SWHSI. Data for this participant were excluded from all data summaries and analysis as they were randomized in error. Thus, 40 eligible participants were randomized, 19 to NPWT and 21 to usual care. The flow of participants through the trial is shown in Table versus 7 days respectively), and had a higher incidence of wound infection (8 of 21 (38 per cent) versus 5 of 19 (26 per cent)), as assessed by clinicians against a predefined features list .Baseline characteristics were similar in the two groups Table . The meaOf the 248 patients screened, 63 (25·4 per cent) were found to be eligible. Common reasons for ineligibility included having already or previously received NPWT on the SWHSI , which was often applied in theatre at the time of surgery (31 patients), and the wound not being suitable for NPWT .Of the 63 eligible patients, 41 (65 per cent) consented to participate in the trial. A variety of reasons for non‐participation were observed, the most common  being that the patient did not wish to receive NPWT.Of the 40 eligible randomized participants, two were fully withdrawn from the trial due to amputation of the reference wound (at 24 and 60 days after randomization), equating to a withdrawal rate of 5 per cent (2 of 40). Both participants were allocated to usual care. The study protocol was subsequently revised to enable continued data collection from participants after amputation, provided they continued to give consent. No further participants, however, underwent amputation.Participants received between one and 12 assessment visits after randomization , with the first postrandomization assessment occurring between 4 and 33 days . Overall, participant self‐completed questionnaire response rates were at least 78 per cent (31 of 40) at all time points.Of the 19 participants allocated to receive NPWT, two never received the intervention. In one patient this was because it would have delayed hospital discharge, and in the other because a NPWT device was not available in the community at the time. Ten participants received NPWT within 24 h of randomization and 14 within 48 h. The primary reason for delay (receiving NPWT 24 h or more after randomization) was the machine being unavailable (6 of the 7 remaining patients).A Renasys® machine was applied in 12 of the 17 participants who received NPWT, PICO® in four and V.A.C.® in one patient. The pressure used ranged between 60 and 125 (median 80) mmHg, and was applied continuously in all but one patient . In addition, two participants treated with PICO® NPWT were reported to have had their wounds packed with Aquacel®  (hydrocolloid) and dressed with an Opsite® (Smith & Nephew) (vapour permeable) dressing.Participants in the intervention group received NPWT for a median of 18 (range 0–72) days. Two of the 19 participants ceased NPWT therapy on the day of randomized treatment receipt due to a failure to maintain the seal. Other reasons for discontinuation of NPWT included: wound improving (8 patients) and wound healed, wound deteriorated, wound bed prepared, wound too dry, wound too small, wound edges bleeding, and blood in tubing of canister (1 patient each).Among the 21 participants receiving usual care, hydrocolloid dressings were the most common initial treatment (11 patients). Other initial dressings included silver‐containing dressings (3 patients), iodine‐containing dressings (3), basic dressings (3) and a soft polymer dressing (1). Five participants in this group subsequently crossed over from their initial dressing to NPWT, a median of 4 (range 0–17) days after randomization. Reasons for crossing over included: improved exudate management and reduced frequency of dressing change , wound deterioration , that the wound bed was prepared for further treatments, for example skin grafting , and that wound healing was not progressing . These five participants remained on NPWT for a median of 31 (range 19–36) days. No other participants in the usual care group were reported to have had NPWT applied during the course of the trial.Of the eight research nurses involved in the study, six indicated that, as part of their role, they would apply NPWT for study participants. Not all the nurses had the opportunity to do this during the trial, but of those who indicated they would have to apply NPWT to study participants, four felt they had received sufficient training, through their institutions, to apply this treatment confidently. All eight research nurses completing the questionnaire indicated that not all of their colleagues had the required knowledge and skills to use NPWT, and that specific standardized training in NPWT application would be required as part of a definitive RCT.Agreement on the assessment of wound healing status  by two initial reviewers was achieved for 29 (73 per cent) of the 40 participants . After assessment of the remaining 11 participants' final photographs by a third reviewer, agreement between two reviewers was reached for 38 participants (95 per cent), but for two (both in the NPWT group) each reviewer recorded a different judgement . Where the reviewer was unsure and a reason for this was provided (8 photographs), it was primarily due to poor photographic quality (4). Overall, eight of the 40 wounds (20 per cent) were judged by the assessors to have healed ; seven of these were also recorded as healed by the investigators at the weekly to fortnightly visits. For three additional wounds judged as healed by the investigators the blinded assessors were either unsure of healing status or there was discordance between all reviewers.Assessors correctly identified treatment allocation using the week 1 photograph for 15 of the 40 participants . Allocation to NPWT was identified incorrectly in six cases.Table S1, supporting information).Twenty‐six participants  consented to be sent a weekly text message asking about their pain, and 20 provided at least one response (10 in each group). The majority of participants who responded provided at least four responses (19 of the 20 responders), and eight responded to all text messages sent. The overall mean pain score reduced between week 1 (mean(s.d.) 4·0(3·0)) and month 3 (mean(s.d.) 1·6(2·0)), although fluctuations in scores were observed during this time interval .Over the course of the trial, the wounds of ten (25 per cent) of the 40 participants were deemed to have healed based on the non‐blinded research nurse assessments at the weekly to fortnightly visits  . The Bland–Altman plots indicate that measurement of the wound using a ruler without adjustment (length × width) overestimates wound area compared with using the tracings . Adjusted wound area measurement (length × width × 0·785) showed better agreement with the tracings, but still tended to overestimate the area . In both cases, overestimation tended to increase with wound size.In general, wounds appeared to decrease in size in both treatment groups at a similar rate over time  score was observed over time in both groups. The Mental Health Composite Scale (MCS) score increased in the usual care group between randomization and 1 month, but decreased  slightly at the 3‐month follow‐up. In the NPWT group, MCS score declined over time . The mean(s.d.) number of dressing changes for NPWT participants was 27·26(18·91), and that for usual care participants was 29·38(14·38).Wound infection was observed, through clinical review against a predefined features list, in 17 participants . In total, 13 participants had a wound infection reported at baseline; in nine the infection resolved and did not reoccur , and in four the infection resolved but later reoccurred . Four further participants developed an infection at some point during their postrandomization follow‐up .Duration of hospital stay data were collected using participant‐reported questionnaires. Eight participants in the NPWT group reported spending nights in hospital during the trial (median 29 (range 2–60) nights). Only one participant in the usual care group reported spending nights in hospital (10 nights).Five serious adverse events were reported, two in the NPWT group from one participant, and three in the usual care group from two participants. All events were related to hospitalization , and only one  was reported as related to the reference wound. No events were deemed to be definitely related to treatment received, but three of the five events  were possibly or probably related, all of which were expected. There were no unexpected serious adverse events.Twenty‐eight non‐serious adverse events were reported. The majority (25) were related to the reference wound, and most (19) were reported as definitely related to treatment . The most common event type was ‘other’ (12 events), which included events such as skin irritation (3), dressing falling off (3) and pump failure (8).Tableversus €931·50(2517·12) for usual care. Conversely, primary and community care costs were lower for the NPWT group; for costs related to GP and nurse visits, NPWT cost a mean of €291·18 (95 per cent c.i. −611·34 to 27·60) less per patient in comparison with usual care.Participants in the NPWT group reported more hospital care and general practitioner (GP) visits, but fewer nurse visits (at surgery or home) in relation to the wound than those in the usual care group; this was reflected in the associated wound‐related costs of each group Table. The meaversus 0·54(0·08) in the usual care group). At 3 months, after adjustment for baseline utility, scores had improved: scores were 0·49(0·35) and 0·77(0·23) respectively. EQ‐5D‐3L™ data were missing for three participants in the NPWT group, so could not be included in the analyses. This, in combination with the small sample size, accounts for differences in the mean scores between the groups at baseline.The baseline EQ‐5D‐3L™ score was lower (worse HRQoL) for participants receiving NPWT (mean(s.d.) 0·34(0·10) Participants who received NPWT had higher total NHS and healthcare costs, and also achieved lower QALY gains than those receiving usual care . To account for the levels of missing data observed for EQ‐5D‐3L™, multiple imputation analysis was conducted; results were similar to those for the complete case analysis .This pilot study has provided invaluable information on the feasibility of conducting a large‐scale trial of NPWT for the treatment of SWHSI.versus usual care in this patient population. A full trial would, however, need to identify a sufficient number of recruiting sites. For example, based on the recruitment rate observed (2 patients per site per month), a minimum of 11 study sites would need to be opened to recruit 400 participants to a similar trial over an 18‐month period. Sample size calculations would also need to consider the impact of (and adjust accordingly for) the rates of participants allocated to but not subsequently receiving NPWT (2 of 19 in the present study) and usual care crossover rates (5 of 21 in this study).After the opening of all sites to recruitment, the consistent rate of recruitment observed indicates that it is possible to recruit participants to a trial of NPWT The majority of the 40 participants had a wound located on the foot , probably because this patient group was more readily able to be recruited to this pilot feasibility study. Existing enthusiasm for NPWT may have produced a lack of equipoise at the study sites involved, with some health professionals being unwilling to include their patients in the study. Thus, some patient subgroups could not be recruited and are under‐represented in this sample. Careful engagement of surgeons in advance of a full trial would be required to ensure equipoise, and thereby promote recruitment. The nature of engagement would depend on whether a homogeneous or heterogeneous study population was proposed for inclusion in the trial.The choice of study population for inclusion in a larger trial would need to be considered carefully, given the heterogeneity of the population of patients with SWHSI. Even within subpopulations, for example those with foot SWHSI, their heterogeneous nature must be considered. Future trials should consider how best to balance ease of recruitment, by including a heterogeneous population, and comparability of data, by focusing on a smaller subpopulation.For this pilot feasibility study, the majority of participants were recruited in acute care settings, as this is where patients with complex wounds are routinely cared for initially. A future RCT may therefore benefit from targeting recruitment in acute care settings initially. The distribution of participants in acute and community settings may differ between individual localities, so before recruitment it would be necessary to ensure that appropriate recruitment strategies and pathways were identified and implemented at individual sites.The most frequent reason for study ineligibility was patients previously or currently receiving NPWT on their SWHSI. A future trial should aim to recruit study sites where there is sufficient equipoise in treatment of patients with SWHSI; thus site evaluation before site inclusion would be essential. Additionally, before undertaking a full RCT, promotional activities with clinicians and research groups to engage surgeons and nurses within the study site would be valuable to ensure consistent and continued referrals into the study. Such work may also help to allay resistance to trial recruitment from certain clinical groups. Anecdotal evidence from the sites in this pilot study suggested some resistance to recruitment of patients by some surgeons, either because NPWT was used primarily for wound management, as opposed to healing, or due to surgeons' prior experience of NPWT, leading them to believe this treatment was inappropriate for use in a specific patient group. Given the small number of sites included in this pilot study, it is impossible to draw firm conclusions on whether resistance amongst specific clinical groups would be present in a larger RCT.versus usual care.A participation rate of 65 per cent, participant‐reported questionnaire response rates in excess of 75 per cent, and a limited number of withdrawals demonstrate that eligible patients are willing to engage and commit to a RCT of NPWT During the study, only two of the 40 participants were withdrawn from the trial, both due to amputation of the reference wound. Data collection did not continue for these participants, and the trial protocol was subsequently amended to reflect that clinical data would cease at the point of amputation. Participant‐reported and resource use data could continue to be collected, subject to continued consent, to capture the impact of limb amputation on patient HRQoL and costs incurred. A future trial should ensure that the process for continued data collection following amputation is clearly defined before commencing study recruitment.The movement of patients between acute and community settings did not affect follow‐up completion, with follow‐up continuing as planned in the majority of cases. The research nurses did, however, note that on occasion it was impossible to assess the wound at follow‐up visits, primarily as a result either of community healthcare professionals (such as district nurses) having already attended and redressed the wound or of community healthcare professionals not attending at the agreed time for the visit, so that research data could not be collected in full.In general, participants received NPWT delivery within 48 h of randomization; however, three participants did not receive NPWT within this time. Two participants did not receive NPWT at all, due to lack of intervention availability and potential for delays to discharge. The availability of NPWT devices should be established at sites from the outset of a future RCT to ensure timely delivery of the intervention.As evidence for the effectiveness of specific wound dressings is limited, and often of low quality, the choice of dressings for use as a comparator within a trial setting requires consideration. Given the number of changes made to the types of dressing used for individual patients in routine care, and differences in guidelines and dressing availability in individual NHS trust settings, it is likely to be difficult to standardize to a single dressing. It may therefore be more pragmatic to consider permitting the use of any dressing, or a specific range of dressing types, in a future trial.Treatment crossover was recorded for five of the 21 participants in the usual care group. In view of the impact that crossover may have in relation to estimates of effect, future trials should consider whether use of NPWT can be minimized or prevented in the usual care arm. If it cannot be prevented, appropriate statistical analysis should be used to account for this crossover.Nurses involved in the study reported that they had received sufficient training within their individual institutions to apply NPWT confidently. They noted, however, that clinical colleagues were not always confident in using NPWT, which corresponds to findings from a recent qualitative studyThis study has demonstrated that collection of data regarding future potential primary and secondary clinical outcome measures is feasible; no major obstacles were encountered. Given the limited number of participants involved in this study, there was insufficient power to enable any true treatment effect of NPWT to be assessed, and, indeed, this was not the purpose of the study. The associations between co‐variables and wound healing obtained using Cox proportional hazards regression should be interpreted with caution. A full RCT is required to assess fully the clinical and cost‐effectiveness of NPWT as a treatment for patients with SWHSI.et al., unpublished data, 2018) preceding this pilot RCT identified a median time to healing for all patients of 86 days. As a result it was deemed that follow‐up of 90 days might be sufficient to observe wound healing. As only ten (25 per cent) of the 40 wounds healed during the course of this trial, a 3‐month follow‐up is probably inadequate for reliable investigation and comparison of healing rates. Follow‐up for a minimum duration of 6 months would therefore need to be considered for a larger trial.Observational work  may be explained by the greater proportion of participants with foot and leg wounds recruited to the trial . The differences in healing trajectory for specific wound types and the complexities associated with wound healing in people with diabetesThe difference in time to healing found in this pilot feasibility trial and a previous cohort study , blinded assessment can be deemed to be feasible and appropriate within a future RCT. Previous venous leg ulcer studiesversus usual care in patients with SWHSI. A full RCT will aim to obtain more definitive evidence and so reduce the current uncertainty surrounding NPWT efficacy and cost‐effectiveness.This pilot study has identified key elements and recommendations for recruitment, data collection, outcome measurement, trial design and safety reporting that should be considered for a larger RCT to investigate the clinical and cost‐effectiveness of NPWT Appendix S1. Clinical assessment of wound infectionTable S1. Wound pain collected using weekly text messages by randomized group and time pointTable S2. Coefficients from the Cox proportional hazards regression models for time to healingTable S3. Wound area from tracings by randomized group over timeClick here for additional data file.


Injuries are a leading cause of death and disability around the world. Injury incidence is often associated with socio-economic and physical environmental factors. The application of geospatial methods has been recognised as important to gain greater understanding of the complex nature of injury and the associated diverse range of geographically-diverse risk factors. Therefore, the aim of this paper is to provide an overview of geospatial methods applied in unintentional injury epidemiological studies.Nine electronic databases were searched for papers published in 2000–2015, inclusive. Included were papers reporting unintentional injuries using geospatial methods for one or more categories of spatial epidemiological methods . Results describe the included injury cause categories, types of data and details relating to the applied geospatial methods.n = 36), falls (n = 11), burns (n = 9), drowning (n = 4), and others (n = 7). Grouped by categories, mapping was the most frequently used method, with 62 (93%) studies applying this approach independently or in conjunction with other geospatial methods. Clustering/cluster detection methods were less common, applied in 27 (40%) studies. Three studies (4%) applied spatial regression methods  to examine the relationship between injury incidence  with aggregated data in relation to explanatory factors .From over 6,000 articles, 67 studies met all inclusion criteria. The major categories of injury data reported with geospatial methods were road traffic  contains supplementary material, which is available to authorized users. Injury is a leading preventable cause of death and disability around the world  guidelines . A comprehensive list of MeSH terms and free text keywords relating to geospatial methods and unintentional injury incidence were used to develop a search strategy .Full text review determined if studies investigated unintentional injuries using geospatial methods to address one or more of the following aims:There was a large number of studies initially included that were subsequently identified as not reporting injury data. In particular, there were a large number of road transport studies that reported data in terms of crashes, collisions or accidents rather than reporting the frequency or rate of the injuries sustained during such events .Data coverage: to identify the source of the data and its geographic location.Name of the GIS package used to analyse the spatial data.Study classification: Studies were classified into one or more of the three broad categories of spatial epidemiological approaches, and relevant details of the methods applied in each category were extracted.Mapping studies: To be classified in this category, studies had to report one or more maps representing raw injury data or results derived from statistical models applied to that injury data for descriptive purposes. The information extracted from each paper included data relevant to the type of map , the summary measure considered  and any smoothing technique  applied.Clustering/cluster detection studies: To be included in this category, studies had to apply one or more methods to the injury data to test for clustering  or to identify clusters . Information regarding each method in terms of its spatial resolution , and approach  were extracted.Ecological studies: To be classified in this category, studies had to apply one or more spatial regression methods to address aetiological questions with the question clearly stated in the study objective. The applied method, as well as the dependent and type of explanatory variables used in the analysis, were extracted.Descriptive data from each study was extracted by the first author   (Bamzar and Ceccato n = 9)        of the included publications. Clustering or clustering detection methods were used in 40% (n = 27) and spatial regression methods for ecological analysis were applied in only 4% (n = 3) of studies. As Table n = 46, 67%) reported only one analysis approach, most commonly mapping, but 18 (27%) used two approaches and three (4%) studies reported all approaches.Mapping was the most common approach applied to the geospatial data, being reported in 93% , falls (n = 10), burns (n = 9), drowning (n = 4), occupational (n = 2), aviation-related (n = 2), dog-bite (n = 1) and natural disaster (n = 1). Of the mapping studies, 15 studies presented dot maps of specific injury locations, 50 studies presented summary measures of aggregated data in choropleth (n = 47) and classed symbol (n = 3) maps. Three of the included studies presented two types of maps (dot and choropleth) so the sum of this group is not equal to the total number of studies . The choropleth and classed symbol maps represented different types of summary measures: incidence rate (n = 27), relative risk (n = 10), frequency (n = 8), and standardised mortality ratios (n = 6). One study mapped more than one summary measure, namely, incidence rate and relative risk  does not equal the total number of studies (n = 47) presented choropleth maps.Of the 62 studies identified as using mapping (Table n = 5)  (Eksler and Lassarre n = 3) (DiMaggio n = 1) , falls (n = 6), burns (n = 2), drowning (n = 2), occupational (n = 1) and poisoning (n = 1). In total, eight different clustering/cluster detection methods were used, with 13 studies using >1 method. Four methods  were applied to test for clustering and four methods (Kernel Density Estimation (KDE), spatial scan statistics, LISA and Getis Ord statistics) were applied to identify clusters or hotspots.Table n = 10 studies) was KDE (considered to be a cluster detection method because of its ability to provide evidence of hotspots) which is mostly used for exploratory analysis of hotspots through a density map. The strength of KDE is that it provides evidence of hotspots in the visual form but the results of KDE methods are largely dependent on the bandwidth (search radius) parameter settings.  followed by falls (n = 2) and drowning (n = 1). A commonly used clustering method for point data was NnH (n = 4), which determines clusters as standard deviational ellipses based on model parameters such as the specified threshold distance and minimum number of points to be included.The most frequently used hotspot analysis method for point data (n = 13 studies) was Moran’s I  and GWR (n = 2) frequentist approaches were applied to investigate social and environmental factors associated with road traffic mortality . In addition, because there is a well-recognised and significant public health burden from these injuries, especially for fatal cases, they have long been a high priority for injury data systems development and prevention . There is a possibility that some relevant keywords (eg. space-time) were missed in the search strategy because of the multidisciplinary nature of this area and the use of many colloquial words by those who work in the area. Moreover, it is possible that searching of other databases, such as the transport research international documentation, may have identified some additional relevant papers. However, given the extensive study selection process the studies identified are likely to be a highly representative sample of papers published in this area. If papers were missed, they are most likely from the category 1 studies (i.e. mapping of descriptive data), with no clear methodology indicating application of spatial methods. There is less likelihood that a study from category 2 or 3  will have been missed, as authors of those studies would likely use the more familiar terminology in formal publications. Therefore, the major findings are unlikely to be influenced by any missed publications.It should be noted that although we have categorised the studies into three distinct categories of spatial epidemiological approaches, this was to simplify the presentation of these results and understanding by a non-technical audience. In reality, these categories occur more along a continuous process rather than as discrete steps (Colantonio et al. The aim of this review has been to provide an overview of the types of geospatial methods applied to unintentional injury epidemiological studies. This study does not provide detail of the analytical processes or steps involved in cluster detection or the spatial regression methods identified. The interested reader is advised to consult key references for specific methods that have been presented throughout the paper (including Anselin .This review has demonstrated that the application of geospatial methods to investigations of unintentional injuries has increased over recent years, but is still relatively uncommon. The majority of studies applying geospatial methods have focused on road traffic injuries. However, other injury cause categories, particularly falls and burns, have also started to make use of geospatial methods in recent years. Mapping was the most commonly used approach for visual display of injury incidence rates. Where applied, cluster detection methods have identified statistically significant spatial dependency within the injury data under investigation. In such cases, the use of spatial regression techniques are needed to minimise the effect of spatial autocorrelation. Geospatial methods are rapidly emerging as an accessible tool for injury researchers to better understand complex injury aetiology but to date, few authors have made use of their full potential in the major injury cause categories.


Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against  Trypanosoma brucei. HAT is a serious health concern in sub‐Saharan Africa with >65 million people at risk and with an annual mortality rate of approximately 9000 per annum.T. brucei as potential lead compounds in the quest for new and effective treatments for HAT.Neglected tropical diseases remain one of the largest concerns in the developing countries of Africa and the South Americas, both in terms of healthcare provision and financial impact on the economies of the world′s poorest countries. This ongoing threat has arisen from a lack of effective prevention methods and minimal financial incentive to develop new therapeutic agents.Annonaceae species, typically found in tropical regions of West Africa and South America.Uvaria chamae, chamuvarinin 1, displayed high levels of cytotoxicity toward the KB3‐1 cell line (IC50=0.8 nm).1 to exhibit unexpected trypanocidal activity in both the bloodstream and procyclic forms of T. brucei ,e Scheme . Synthestert‐butylhypochlorite was essential as the oxidising agent.9–13  found that 3 Scheme . Yields T. brucei are outlined in Table T. brucei being maintained to the original triazole analogues. The THP stereochemistry had a significant influence on potency with the syn–syn compounds 9 and 10 and anti–anti13 most potent. This is in contrast to our original triazole series where anti–anti analogues were generally inactive.T. brucei over mammalian HeLa cells, with all but one of the analogues greater than 100 μm against HeLa cells.Screening results for our compounds against procyclic and bloodstream forms of 14–16 in useful quantities . The selectivity observed in this instance merits further detailed study of this unusual heterocyclic framework.Screening of these compounds revealed that furoxans also displayed encouraging ls Table , entry 2T. brucei and excellent selectivity over mammalian cells in certain cases. These selectivities are a significant improvement over our previously described triazole compounds and can serve as a basis for further optimisation. Current efforts are focused on other heterocyclic spacers as well as the synthesis of fluorescent and affinity tagged versions in order to isolate target protein(s) allowing us to establish the trypanocidal mode of action.We have demonstrated the utility of our chiral THP building blocks by their elaboration to oximes and their use in ‘Click’ reactions with alkynes to generate complex isoxazole products. Moreover, dimerisation of these oximes allows access to furoxan and furazan heterocycles. All series tested show encouraging low micromolar activity in As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Trans‐equatorial long‐distance migrations of high‐latitude breeding animals have been attributed to narrow ecological niche widths. We suggest an alternative hypothesis postulating that trans‐equatorial migrations result from a possible increase in the rate at which body stores to fuel migration are deposited with absolute latitude; that is, longer, migrations away from the breeding grounds surpassing the equator may actually enhance fueling rates on the nonbreeding grounds and therewith the chance of a successful, speedy and timely migration back to the breeding grounds. To this end, we first sought to confirm the existence of a latitudinal trend in fuel deposition rate in a global data set of free‐living migratory shorebirds and investigated the potential factors causing this trend. We next tested two predictions on how this trend is expected to impact the migratory itineraries on northward migration under the time‐minimization hypothesis, using 56 tracks of high‐latitude breeding shorebirds migrating along the East Asian‐Australasian Flyway. We found a strong positive effect of latitude on fuel deposition rate, which most likely relates to latitudinal variations in primary productivity and available daily foraging time. We next confirmed the resulting predictions that (1) when flying from a stopover site toward the equator, migrants use long jumps that will take them to an equivalent or higher latitude at the opposite hemisphere; and (2) that from here onward, migrants will use small steps, basically fueling only enough to make it to the next suitable staging site. These findings may explain why migrants migrate “the extra mile” across the equator during the nonbreeding season in search of better fueling conditions, ultimately providing secure and fast return migrations to the breeding grounds in the opposite hemisphere. Migration has evolved as an adaptation toward avoiding risks, such as unfavorable thermal conditions, food shortage, predation, and disease, as well as seizing opportunities where and when they arise  a northward migrant heading to breeding grounds in the Northern Hemisphere from sites in the Southern Hemisphere will use big jumps that will take it to an equivalent or higher latitude in the opposite hemisphere in order to reach high‐quality staging sites and skip low‐quality sites in the tropics; and (2) once having passed the equator, the migrant will use small steps, and fuel sufficiently only to make it to the next suitable staging site (to avoid the energetic cost of carrying excessive amounts of fuel). If these predictions are true, it may be beneficial to spend the nonbreeding season away from the equator at higher latitudes in search of better fueling conditions. Although thus covering a longer distance, this longer journey may result in a higher net speed of migration during the return migration to the breeding grounds.The aim of this study was to comprehensively investigate (1) the effect of latitude on fueling rates in different migratory shorebirds at a global scale; (2) investigate the potential underlying factors relating to such a pattern with respect to latitude, that is (i) total intertidal biomass in different sites worldwide as an estimation of prey availability and (ii) primary productivity (measured using chlorophyll a concentration); and (3) examine whether our assumptions of a latitudinal pattern in fueling rates lead to the above predicted (1–2) migration strategies using satellite transmitter data and geolocation dataloggers (“geolocator”) data for three high‐latitude breeding shorebird species migrating along the East Asian‐Australasian Flyway.−1) and lean body mass data for migratory shorebirds were collected from the literature for different geographical locations  data   worldwide were collated . These primary productivity data were remotely estimated as a function of chlorophyll a, available light, and the photosynthetic efficiency averaged over 8 days. These descriptions are based on the vertically generalized production model (VGPM)  was downloaded from Ocean Productivity  and in Victoria and Tasmania (ruddy turnstone). Of the 56 tracks available for ruddy turnstone, five have been published previously, and details on these tracks can be found in Minton et al. , we used general linear modeling with both latitude and latitude squared as dependent variables  to examine the effect of latitude on fueling rates, primary productivity and total biomass.Interspecific variation in body mass has been suggested to affect fueling rates .Reaching the target destination (breeding grounds), the remaining flight distance to that target, becomes progressively shorter. Under the assumption that birds will follow the shortest route to their ultimate target, when plotting leg flight distance against latitude, it was expected that leg flight distances would fall on or below the line depicting the shortest distance between the departure staging site and the ultimate target. For regressions between flight distance and latitude, All statistical analyses were conducted using R version 3.0.3  .Based on general linear modeling, latitude had a significant effect on fueling rates only in its quadratic form (01) Fig. A, suggesγ = 0.0002; PMCMC < 0.001). Contrastingly, however, body mass had no additional significant effect on fuel deposition rate.Accounting for phylogenetic effects using a phylogenetic mixed model, we found that again fueling rates were positively correlated with latitude only in its quadratic form , thus confirming a U‐shaped relationship with latitude , whereas latitude in its linear form had a significant effect . This implies that a latitudinal trend exists from south to north and not a U‐shaped relationship as we had predicted , sanderling , bar‐tailed godwit from the subspecies baueri , and menzbieri   when leaving staging sites at temperate Southern Hemisphere latitudes, followed by relatively shorter hops/skips toward the final destination, their Arctic breeding grounds. These shorter hops/skips after a major jump may be a result of fine‐tuning timing of arrival at the breeding grounds. However, according to the time‐minimization hypothesis, the long initial jump across the equator followed by shorter hops/skips may also result from a specific pattern in the potential for fuel deposition along the birds' flyway. Using an extended data set on fueling rates and flight distances derived from the literature and from geolocator and satellite transmitters, we confirmed earlier suggestions of a latitudinal trend in fueling rate in shorebirds, where fueling rates decrease from high to low latitudes in the Northern Hemisphere , latitudinal trends have been shown in (surface) prey biomass . Indeedand Król  found inData on flight leg distance in relation to the latitude of the departure site Fig.  confirmeLow fueling rates may not be the only factor stimulating some migrants to avoid sites at low latitudes around the equator. At various locations across the globe, a number of shorebird studies have found disease prevalence to be negatively correlated with absolute latitude  may also be of particular importance for the successful completion of migratory journeys (Aharon‐Rotman et al. The latitudinal pattern in the suitability of staging sites for migratory fueling confirmed here may have been of great importance in the evolution of migratory strategies. This is highlighted by the migration itineraries of some shorebird species None declared.Appendix S1. Phylogenetic tree used for the phylogenetic mixed model, pruned from Thomas et al. (s et al. .Click here for additional data file.Appendix S2. A summary of fuel deposition rate data collected from the literature.Click here for additional data file.


To assess what is known about the relationship between patient experience measures and incentives designed to improve care, and to identify how public policy and medical practices can promote patient‐valued outcomes in health systems with strong financial incentives.Existing literature (gray and peer‐reviewed) on measuring patient experience and patient‐reported outcomes, identified from Medline and Cochrane databases; evaluations of pay‐for‐performance programs in the United States, Europe, and the Commonwealth countries.We analyzed (1) studies of pay‐for‐performance, to identify those including metrics for patient experience, and (2) studies of patient experience and of patient‐reported outcomes to identify evidence of influence on clinical practice, whether through public reporting or private reporting to clinicians.PRI), each with distinctive roles shaping clinical practice: (1) patient‐reported outcomes measuring self‐assessed physical and mental well‐being, (2) surveys of patient experience with clinicians and staff, (3) narrative accounts describing encounters with clinicians in patients' own words, and (4) complaints/grievances signaling patients' distress when treatment or outcomes fall short of expectations. Because these forms vary in crucial ways, each must be distinctively measured, deployed, and linked with financial incentives. Second, although the literature linking incentives to patients experience is limited, implementing pay‐for‐performance systems appears to threaten certain patient‐valued aspects of health care. But incentives can be made compatible with the outcomes patients value if: (a) a sufficient portion of incentives is tied to patient‐reported outcomes and experiences, (b) incentivized forms of PRI are complemented by other forms of patient feedback, and (c) health care organizations assist clinicians to interpret and respond to PRI. Finally, we identify roles for the public and private sectors in financing PRI and orchestrating an appropriate balance among its four forms.First, we identify four forms of “patient‐reported information” (Unless public policies are attentive to patients' perspectives, stronger financial incentives for clinicians can threaten aspects of care that patients most value. Certain policy parameters are already clear, but additional research is required to clarify how best to collect patient narratives in varied settings, how to report narratives to consumers in conjunction with quantified metrics, and how to promote a “culture of learning” at the practice level that incorporates patient feedback. The past two decades have seen the emergence of several strategies for improving quality and efficiency in medical care. Chief among these have been (1) a renewed focus on how health care is experienced by patients through the promotion of “patient‐centered care” and (2) efforts to refine the financial incentives designed for health care providers through “pay‐for‐performance” initiatives.Making health care more patient‐centered requires collecting patient‐reported information about health and health care in comprehensive, reliable ways. Initial efforts focused on developing standardized metrics of patient experience. While collection of such standardized measures has helped to identify areas for improvement and motivate changes in practice, these efforts also have highlighted some of the limits of standardized close‐ended questionnaires and the need to supplement surveys with open‐ended narrative accounts   or consumerism in general .Various forms of patient‐reported information have been introduced to American medicine over the past 40 years :In the contemporary American health care system, there is a mix of these four forms of patient‐reported information. The past decade has seen a steady increase in the collection and public reporting of patient‐reported outcomes, facilitated by the development of national databases such as the Patient Reported Outcomes Measurement Information System  payments to physicians  based on data submitted through the Centers for Medicare and Medicaid Services (CMS) Physician Quality Reporting System. The CAHPS Clinician & Group (CG‐CAHPS) Survey will be included among the measures used to assign physicians to cost/quality tiers.Heath plans and medical groups already have begun implementing value‐based purchasing based in part on patient experience measures. Blue Cross and Blue Shield of Massachusetts (BCBSMA), for example, developed an “Alternative Quality Contract” in 2007 that combines clinical and patient experience measures to establish performance targets for both inpatient and ambulatory service providers. Health Plus of Michigan, a health plan serving commercial, Medicaid, and Medicare enrollees, introduced a pay‐for‐performance program for its PCPs in the same year, based partially on CAHPS scores.Patient experience also has been incorporated into pay‐for‐performance initiatives abroad, though typically in a modest role. In the Quality and Outcomes Framework deployed in the United Kingdom, for example, the “patient experience” domain for primary care includes two measures: one based on survey results, the other on the average time spent with patients. But these are only two out of 146 measures linked to incentives.The multiple ways medical care can be assessed and described through the eyes of patients have given rise to a complex, confusing, and poorly defined array of measures and strategies. This is evident from their representation in the health services literature. For example, the CAHPS surveys were explicitly designed to substitute reported experiences for satisfaction scores to avoid expectational biases, yet they are routinely described as and lumped together with “patient satisfaction” surveys. A similar muddling occurs with patient “complaints,” a term used indiscriminately to refer to (1) formal grievances about clinicians filed with third parties; (2) concerns about care that patients express to their own clinicians; (3) negative comments submitted to Internet websites; and (4) patients' low ratings for their clinicians on satisfaction surveys.why we collect information from patients and how we intend it be used for improving clinical practice,To avoid pitfalls created by blurred definitions and to introduce a vocabulary more apt for describing both patient‐reported information (or PRI). This is not a term widely used in the literature: we introduce it here as an umbrella label that emphasizes the breadth and diversity of this information.all forms of feedback collected from patients—whether describing their own health or their experiences with medical care, whether initiated by the patient or elicited by some third party, whether conveyed as free‐form narrative or in response to questions with close‐ended scales. This broad umbrella covers four subsets of information, defined here, for clarity, as mutually exclusive.Throughout this paper, we will refer to all forms of information collected from patients  as Patient reported outcome measures (PROMs) is restricted here to refer to feedback from patients about their health and functional status, measured on a quantified scale.Patient experience measures refer to any feedback from patients about their interactions with clinicians and the health care system, when that information is conveyed as a response to close‐ended  survey questions.Patient comments or narratives refer to any accounts of health care experiences reported in the patient's own words—whether written or spoken in a phone interview. These comments might be voluntarily submitted to a website or collected more systematically, including from open‐ended questions incorporated into surveys that also include close‐ended patient experience measures.Patient complaints will be restricted here to refer to comments that are filed with a third party  regarding some problematic outcome or experience with a clinician. Complaints might be volunteered or elicited by an organization, ombudsman program, or other grievance process.Though we have labeled these four categories as distinct, in practice they are often entwined with one another, as we explore below. We do so in three stages. In the first, we summarize the empirical literature assessing the impact of incentive arrangements on clinicians' response to patient‐reported information, drawing references from Medline and the Cochrane databases. In the second, we extend our purview beyond empirical studies to consider some strategic perspectives on the role of PRI for improving health system performance. We conclude by identifying priorities for future research and policy implications related to the interaction of incentive arrangements and patient feedback.Policy makers have historically undervalued patient experience. Nevertheless, a rapidly accumulating body of evidence makes clear that any sound strategy for broadening and strengthening incentives for clinicians must give primacy to patient experience, because (1) patient experience matters for quality and quality improvement; (2) the quality of patient experience is at risk if not explicitly and carefully addressed in incentive‐based reforms; and (3) if financial incentives are linked to the most appropriate forms of PRI, crafted with appropriate strength, and implemented in ways sensitive to the importance of nonpecuniary inducements for quality improvement, pay‐for‐performance programs can be successfully implemented in ways that protect and promote patient‐valued outcomes.Patient experience has recently been recognized as a cornerstone of improved health care that is distinct from other aspects of quality, as enunciated in influential reports from the Institute of Medicine, the Institute for Healthcare Improvement's “triple aim,” and the Measure Application Partnership established by the PPACA  that clinicians nonetheless might influence  are at increased risk for worsening under conventional pay‐for‐performance arrangements, because they are less readily counted and tracked over time.is specific to patient–clinician interactions. Pay‐for‐performance systems, like other reforms that require real‐time documentation , cause clinicians to focus on their computer screens, to the extent that even “… kind, compassionate, and well‐intended physicians miss … signals” patients may be sending about “depression, disagreement, and lack of understanding” , the pay‐for‐performance system for clinicians in the United Kingdom. These reforms offer a useful benchmark for assessing how “strong” incentives affect clinicians' practice, as they (1) have been in effect for almost a decade; (2) put a larger share of clinician's income at risk than most incentive schemes in the United States,Soon after implementation of the QOF, a clear pattern emerged. Aspects of quality that were incentivized did better than predicted from previous trends, whereas those not incentivized fell below their trend lines  may have distracted them from patient‐led consultations and listening to patients' concerns”  simply collected the data and made them available to clinicians; (2) insisted that individual clinicians have a plan of action responding to patient feedback; or (3) engaged the practice in a collective response to patient experiences. These groups reported strikingly different performance on  simply cControlling statistically for other characteristics of the patients, clinicians, and practice settings,Not all forms of PRI can be directly linked to financial payments. Narrative data, gathered through formal complaints or open‐ended comments on patient experience surveys, are not fully quantifiable yet are essential lynchpins for encouraging clinicians to respond to patient experiences. As noted in a recent study, health care organizations identified as leaders in learning from patient information placed “high value on narrative feedback from patients as a learning tool and reported narratives as a catalyst for change. Interviewees frequently stated that patient stories, whether from qualitative surveys or patient journals, provided important insights not captured by quantitative data”  can be made more influential through financial incentives, if (1) those incentives have substantial value relative to those devoted to clinical outcomes and (2) individual clinicians are assisted in interpreting and responding to patient feedback. Supporting clinicians' learning from patient experience may also improve clinical outcomes.Patient narratives (open‐ended comments and complaints) can be indirectly facilitated through incentives, but more complete clinician engagement requires that financial inducements be augmented with combined public and private reporting.Feedback of patient‐reported information is most effective at changing clinician practices if targeted to individual clinicians rather than medical groups.Although the benefits are clear, integrating PRI with financial incentives faces some substantial challenges. We predicate the strategic perspectives offered below on some observations regarding how information is generated and used in the highly fragmented system that characterizes American health care—these observations are justified further below but are offered here as an initial overview:Multiple forms of PRI make it easy to confuse kinds of information and may lead to initiatives that work at cross‐purposes, undermining the impact of each.Diffused benefits of patient‐reported information weaken the impetus for key stakeholders  to invest adequately in collecting PRI or in leveraging its impact to improve care.A shallow sense of collective identity among patients in the United States leaves them less willing than patients in other countries—where citizens see themselves as beneficiaries of a common system—to participate in initiatives collecting information or learning from others' experiences.Persisting gaps in methods for eliciting PRI reveal the need for more research on how PRI can be measured and fed back to clinicians in varied clinical settings.The need to assist clinicians as they strive to learn from patients' experiences suggests that incentives should target practices as well as individual physicians.Because these issues are interconnected, they must be addressed in unison. What is needed is a broad, strategic vision of how (1) multiple forms of PRI can be most usefully collected and deployed across varied clinical settings, and (2) challenges that currently inhibit optimal use of PRI can be addressed. We offer here a blueprint for such a strategic vision, building on some initial observations about how PRI is currently collected and deployed.Three observations play a central role in developing the strategic plan offered here.attention rather than increase or decrease particular practices. Anticipating the impact of incentives thus requires understanding the ways in which clinicians think as well as act, including the ways in which their decisions and practices are constrained by limited time and attention   both need to be actively elicited to ensure a representative set of accounts  an electronically mediated, adaptable system for repeated collection of symptoms and functional outcomes; (2) a real‐time grievance system that actively elicits patients' concerns immediately following episodes of care; and (3) periodic surveys collected at strategic intervals to assess patients' experiences with clinicians over a defined time period, combining close‐ended patient experience questions with open‐ended narrative accounts.Public authorities also have a useful role coordinating the deployment of PRI‐based interventions. Information collected from patients can be used to induce changes in clinical practice in three ways: by directly linking to financial incentives , through public reporting (reputation effects), or via private reporting . It is important to identify actors  that can help to orchestrate how different forms of PRI are deployed. For instance, patient experience metrics appear more easily interpreted by consumers than are PROMs; even relatively simple metrics, such as mortality rates associated with cardiac care, have yielded a muted or confused consumer response  senior leadership commitment and engagement; (2) a strategic vision clearly and constantly communicated to every member of the organization; (3) involvement of patients and families at multiple levels; (4) a supportive work environment for all employees; (5) systematic patient experience measurement and feedback reporting; and (6) adequate resources devoted to care delivery redesign Shaller .14 InterThe optimal balance among these attributes will vary for each organization—and therefore is best not dictated by either policy makers or purchasers. Rather, it seems more appropriate to create financial incentives tied to patient experience metrics that work at least in part through the organizations with which clinicians are affiliated: for example, the practice or facility level (for care delivered on an inpatient basis). Staff members at multiple levels in the organization need training in quality improvement concepts and methods that will enable them to effectively make, measure, and manage change Shaller . How besAside from incentivizing the organizations to attend more closely to patient feedback, several other factors appear to promote adoption of a learning culture. Initiatives are more successful when set within quality improvement collaboratives than when they rely on less interactive interventions  the size of the practice and (2) the treatment regime—whether a health problem can be treated by a single clinician or requires coordination among multiple practitioners.Despite the long‐standing trend toward consolidation of physician practices,Size of practice initially seems less relevant for PRI conveyed through narrative accounts. But size may affect the reactions induced by public reporting of comments. Some countries with the longest track records of reporting patient comments have encouraged providers to publicly respond to those comments Trigg . CliniciWhen patients face complex medical problems that require treatment by multiple providers in multiple settings, patient feedback becomes more complicated because it is more difficult for patients to reliably attribute credit or blame  morIn a complex, dynamic health care system, policy interventions can never be fully evidence‐based, because practices and performance vary too much over time and place. We already have sufficient evidence in hand regarding both patient‐reported experiences and pay‐for‐performance reforms to begin the process of integrating them in a more thoughtful manner. More specifically, we favor a more coherent role in the financing and coordinating of PRI for the public sector, implemented in flexible ways to adapt to regional differences in political ideology and local health care markets.The impact of patient feedback is also shaped by existing public policies and programs, as summarized in Table Some of these initiatives can be pursued under existing legislative authority. In its administrative role, the CMS has the discretion to specify the terms under which patient experience data are reported for beneficiaries of Medicare and Medicaid, as well as for consumers insured through the health exchanges. CMS is thus well positioned to test through regional pilot programs how to most effectively integrate qualitative and quantitative feedback on patients' experience. Because there remain a number of questions about how best to collect and disseminate qualitative patient feedback, it seems wisest to rollout these pilots sequentially, so that later initiatives can be informed by what is learned from the first round of pilots.CMS can also fund, under its existing authority, demonstration projects that allow for more local discretion and experimentation, as it has with the development of ACOs and patient‐centered medical homes. State governments, too, can facilitate integration of patient experience into systems with strong health care incentives, building on past collaborations with private sector stakeholders to promote public reporting of quality.Experience to date suggests that states are the most promising catalyst for reforms that encourage a culture of learning from patient experiences within each participating health care organization. Reforms most appropriately enacted by an expanded scope of federal authority include making the federal government primary financier for collecting patient feedback as well as primary regulator of the design of private sector pay‐for‐performance.More effective integration of patient‐reported information into a health care system with strong financial incentives is a feasible and laudable short‐term goal. Such an initiative may also trigger more profound transformations in the longer term. For example:If public reporting arrangements gave as much priority to patient's words as numerical ratings, a subtly humanizing element might be integrated into how Americans think about medical care and induce, over time, yet deeper changes in how we approach accountability and quality in health care settings.If policy makers established a well‐publicized commitment to support the collection and dissemination of PRI, Americans might over time come to believe that patient voice has real legitimacy in health care and policy making. This shift could in turn induce further consumer empowerment and engagement.If new health policies offered sustained support and encouragement for a culture of learning from patient experience, interactions between patients and clinicians would take place in a substantially different context.The shape and direction of such changes cannot be fully anticipated, but we expect that they will be well worth watching—and attending to in future policy refinements.Appendix SA1: Author Matrix.Click here for additional data file.a Brief History of Patient‐Reported Information.Appendix SA2: : a Glossary of Terms Used in This Paper.Appendix SA3Click here for additional data file.


Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV‐1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV‐1 infection. Thus, for the global community to achieve elimination of new paediatric HIV‐1 infections, innovative approaches need to be explored. Immune‐based approaches to prevention of mother‐to‐child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS‐free generation. Immune‐based interventions to prevent MTCT of HIV‐1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune‐based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast‐Track 2030 goals to eliminate new paediatric HIV infections. These challenges have not been mitigated by implementing a simplified approach of universal ART for pregnant/breastfeeding women (Option B+). For example, comparing the antenatal cascade in over 28,000 women presenting to antenatal care in Malawi before and after implementing Option B+ in 2011, although a greater proportion of HIV‐1‐infected pregnant women were enrolled in services and initiated ART, there were significant incremental losses after ART initiation While scale‐up of current ART interventions for prevention is a priority, the addition of immune‐based interventions can assist in overcoming a number of challenges that have been observed to date 2Developing a preventive HIV‐1 vaccine is an enormous challenge that so far has met with only limited success in the RV144 trial in Thailand First, preventive HIV‐1 vaccines will ultimately need to be implemented as part of a routine immunization schedule prior to sexual debut. Including HIV‐1 immunization in the childhood vaccine schedule provides the opportunity for high coverage with a multi‐dose vaccine, as well as long boosting intervals to improve the likelihood of affinity maturation for antibodies. Multi‐dose vaccine strategies have been difficult to implement outside the childhood immunization schedule. For example, immunization coverage for hepatitis B virus (HBV), which is both a sexually and perinatally transmitted pathogen, significantly improved when it was moved from an adolescent vaccine to a neonatal vaccine The infant immune system is often described as immature, but it is more accurate to say that it has a different set of regulatory constraints and capacities. The immune responses of infants and young children are often more robust than adults and may have a broader unmodified repertoire of T‐cells and B‐cells that could more effectively be primed by vaccination Finally, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve Figure . For exa3Initial studies of HIV‐1 hyperimmune globulin in HIV‐1‐infected pregnant women and/or their newborns utilized polyclonal preparations of highly purified human immune globulin containing high titres of antibody to HIV‐1 structural proteins that did not have significant anti‐viral activity, required frequent (monthly) administration, and did not demonstrate efficacy for prevention in studies in the US and Uganda However, the identification of human anti‐HIV‐1 mAbs with high potency and neutralizing breadth, combined with protein engineering to extend half‐life and optimize potency, and advances in mAb manufacturing have made the use of mAbs in prevention of MTCT feasible and practical. In a recent review of potential use of monoclonal antibodies for prevention of sexual HIV‐1 transmission, Anderson and colleagues note that with optimization of antibody manufacturing platforms, bnAbs will be available at a significantly reduced cost in the near future; using their estimated target cost of $10/gram product, the cost for an infant dose of 100 mg could be as low as $1.00 et al. provided additional evidence to support the value of passively administering bNAbs to newborns to prevent HIV‐1 infection Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific mAbs can prevent chimeric simian human immunodeficiency viruses (SHIV) transmission to newborn nonhuman primates The precedent for administering polyclonal and monoclonal antibodies to newborn infants for the prevention of viral disease has been established for HBV and respiratory syncytial virus (RSV), respectively. Indeed, MTCT of HBV at birth has been nearly eliminated in developed countries by administration of birth‐dose intramuscular hepatitis B immunoglobulin and vaccination Figure  32. HowePalivizumab for RSV has been marketed since 1998 and can safely and effectively reduce the frequency of serious RSV disease in high‐risk infants. New generation RSV mAbs with higher potency and extended half‐lives are in the final stages of efficacy evaluation and are being developed for use as a single dose at birth. These examples, together with the data from animal models and the advances in development and manufacturing, suggest that administration of mAbs to newborns at risk of HIV‐1 infection would be an effective and practical adjunct to antiretroviral treatment to prevent MTCT of HIV‐1 at birth and through breastfeeding. This may be especially useful in high prevalence areas with high infection pressure, in situations where there has been limited access to prenatal care, or when HIV‐1 in the mother is diagnosed late.An open‐label, dose‐escalating phase 1 study of safety and pharmacokinetics of VRC01 delivered subcutaneously at birth (P1112 study) is ongoing in babies born to HIV‐1 infected women in USA, South Africa and Zimbabwe Even if one imagines the optimal scenario where 100% of the 1.5 million HIV‐infected women giving birth annually are tested, identified, and initiated on ART prior to the third trimester and transmission rates observed in clinical trials (e.g. PROMISE) are achieved, the residual 1.5% transmission rate would translate to nearly 23,000 newly infected infants born annually. In reality, over 30% of pregnant women do not receive HIV testing; many women in sub‐Saharan Africa only present for antenatal care in the third trimester or at delivery 4The tremendous progress in preventing MTCT of HIV‐1 is tempered by complex remaining health system and societal challenges in many LMIC. In addition to efforts to improve delivery of well‐established interventions, it is important to explore new approaches that may have complementary or even synergistic impact with existing efforts to prevent HIV‐1 transmission to infants The authors declare that they have no competing interests.YV, IJ, GS wrote the first draft. YV, IJ, BSG, CKC, LMM, PMM, SRP, GS edited the manuscript.


Meligethes aeneus). Widespread adoption of best practice in pollen beetle management is therefore needed. Decision support systems (DSSs) that identify the risk period(s) for pest migration can help to target monitoring and control efforts, but they must be accurate and labour efficient to gain the support of growers. Weather data and the phenology of pollen beetles in 44 winter oilseed rape crops across England over 4 years were used to compare the performance of two risk management tools: the DSS proPlant expert, which predicts migration risk according to a phenological model and local weather data, and ‘rule‐based advice’, which depends on crop growth stage and a temperature threshold.The reliance on and extensive use of pyrethroid insecticides have led to pyrethroid resistance in pollen beetle (DSS more accurately predicted migration start and advised significantly fewer days of migration risk, consultation days and monitoring than did rule‐based advice.Both risk management tools were effective in prompting monitoring that would detect breaches of various control thresholds. However, the proPlant expert DSS reliably models pollen beetle phenology. Use of such a DSS can focus monitoring effort to when it is most needed, facilitate the practical use of thresholds and help to prevent unnecessary insecticide applications and the development of insecticide resistance. © 2015 Rothamsted Research Ltd. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.The  Decision support systems enable growers and advisors to determine levels of risk to the crop, monitor appropriately to assess pest abundance and take action if necessary, based on thresholds. Here we seek evidence that use of a web‐based DSS system can improve risk assessment for pollen beetle management in winter oilseed rape (WOSR).TM (http://www.cropmonitor.co.uk/wosr/surveys/wosr‐sprPest_gyb08.cfm), the lower control threshold of 5 beetles plant−1 was breached at only one of 48 WOSR fields sampled across England and Wales, and the standard 15 beetles plant−1 threshold was never attained at these sites. However, in the same year, an average of 0.3 insecticide applications per field were targeted against pollen beetles in oilseed rape in Great Britain.Pollen beetles cause damage to flower buds by feeding in them, resulting in bud abscission and loss of yield.et al.Not only is rule‐based advice that relies on a simple temperature threshold likely to lead to an excessive requirement for monitoring, it is also likely to take insufficient account of the significant factors governing the timing of migration. The 15 °C flight temperature threshold advised in the United KingdomDecision support systems (DSSs) for pest management are computer‐based information systems that assist the grower in decision‐making in crop protection. They may incorporate models of pest phenology and/or damage risk, are parameterised by multiple variables, and they generate risk assessments and other information upon which the grower can act. When implemented effectively, they can improve crop protection and minimise the input and cost of pesticides.http://www.proplantexpert.com) is a web‐based DSS developed in Germany that alerts the user to the start of pest migration and its progress. It provides local 3 day forecasts of pest migration risk and indicates days when crop monitoring is needed. proPlant expert's forecasts are based on phenological models developed from historical data on pest abundance in crops and a sophisticated use of weather variables.http://www.bayercropscience.co.uk/ , reflecting the range of control thresholds currently recommended in different European countries.22.1et al.The phenology of the beetles on winter oilseed rape crops in spring was assessed on a total of 169 commercially managed fields in the United Kingdom during March to early May in 2008–2011, as part of a project to develop an integrated pest management strategy for the control of pollen beetles.−1).−1 was included to reflect the lower range of thresholds in current use in European countries.For this study, a subset of 44 fields in eastern and central England were chosen  . These fields were selected because pollen beetles were monitored both on plants and on sticky traps approximately twice weekly during the green‐to‐yellow bud stage (BBCH growth stages 51 to 59), the period during which WOSR is susceptible to pollen beetle damage.The frequency of monitoring requested was minimised (to twice weekly) in the interests of encouraging wide participation of volunteers, and it was therefore necessary to estimate some phenological parameters. The period when plants in each field were at the bud development growth stages (51 to 59), delimiting the period when plants are at risk of pollen beetle damage, was estimated by interpolation from growth stage data recorded on the twice weekly monitoring dates, taking into account the progression of growth stages at other sites in the same year. It was assumed that any breach of a pollen beetle threshold took place on the monitoring date on which it was observed. This conservative assumption is independent both of the risk management tool used (rule‐based advice or DSS) and of the weather data on which they were based. Any consequent delay in the recognition of a threshold breach is likely to affect the performance assessment of each management tool equally.2.2−1).Weather data were obtained from the UK Met Office or from farmer‐operated meteorological stations within 1–80 km (average 16 km) of each sampled field. The proPlant phenological model requires daily measurements of minimum and maximum air temperature (°C), average air temperature (°C), rainfall (mm), sunshine (h) and average wind speed  separately. For each site and for each risk management tool, the dataset was delimited by the period between growth stage 51 (or the start of field monitoring if later) and the day any breach of threshold would have been detected had the advice of the management tool been followed. If no threshold breach was detected, the whole period from growth stages 51 to 59 was included. Observations following any spring insecticide applications were excluded from the analysis.The performance of the two risk management tools was compared for each of the three selected control thresholds  was counted. Days with significant migration risk were taken to be all those with a maximum temperature of ≥15 °C for rule‐based advice and all those with yellow or red dots for the proPlant expert DSS.Forecast consultation. The number of days when a weather forecast consultation or a DSS forecast consultation was advised during growth stages 51 to 59, up to the dates that any threshold breaches would be detected, was counted. For rule‐based advice, all days during the susceptible plant growth stage (51 to 59) were taken to be ‘forecast consultation days’, i.e. days when the weather forecast should be consulted to determine whether the temperature was likely to reach 15 °C. DSS forecast consultation days were designated according to the following proPlant guidance: the DSS should first be consulted on the day that crop growth stage reaches 51; thereafter, it should be consulted either every third day or on any day when a coloured dot on the migration bar has been indicated by a previous consultation, whichever is more frequent; the final proPlant expert consultation should be made on the day after migration is predicted to be complete or consultation should cease at flowering, whichever is earlier.Crop monitoring. The number of crop monitoring days advised during growth stages 51 to 59, up to the dates that any threshold breaches would be detected, was counted. For rule‐based advice, all days with a maximum temperature of ≥15 °C during growth stages 51 to 59 were taken to be monitoring days. The DSS proPlant expert indicates specific monitoring days on its user interface (see Section 2.3.1 above).Number of days when significant migration risk, forecast consultation or crop monitoring were advised.Several performance measures were compared for ‘rule‐based advice’ and for the proPlant expert DSS:2.4.2The number of days of migration risk advised, the number of consultation days advised and the number of monitoring days advised prior to each threshold breach were analysed using bivariate mixed models, accounting for variation between sites and years. For the comparison of the real‐time performance of rule‐based advice and the DSS, analysis of variance was used. Both analyses were done using GenStat, v.14 .33.1−1 threshold was breached at only one site, the 5 and 2 beetles plant−1 thresholds were breached at 19 and 36 sites (43 and 82%), respectively; sufficient to provide a good test of the performance of each management tool.The mean duration of the comparison of risk management tools at the 44 sites included in the study was 17 days, and the mean interval between field samples was 3.7 days .The detection of breached thresholds would have been slightly delayed using the DSS as opposed to rule‐based advice  than did rule‐based advice (days with a temperature of ≥15 °C). At the 2, 5 and 15 beetles plantReal‐time analysis The comparison of real‐time advice and a posteriori advice at nine sites in the Bedford area in 2011 supported the results of the main analysis and validated the a posteriori approach. At almost every threshold level and both in real time and a posteriori, the DSS proPlant expert advised fewer days of good migration conditions, fewer days of forecast consultation and fewer pollen beetle monitoring days than associated with rule‐based advice  takes into account more weather variables than the temperature‐based rule system we used in comparison. For example, a day might be warm enough for migration but too windy. The proPlant expert DSS also gives the user early warning of potential risk, indicating the earliest date that migration could start. In this study, proPlant expert's first migration risk warning consistently preceded or accompanied the first pollen beetles sampled on crops or on sticky traps. The date of the first proPlant expert dot preceded the first beetle caught by an average of 9.5 days in this study (supporting information Table S1). This could assist forward planning for growers and advisors, especially those using monitoring traps to determine local movement of pollen beetles or their abundance.−1 threshold must be less than if migration were only 40% complete. The user might decide that the need for control is so unlikely when migration is 90% complete that no further monitoring is needed.The phenological model underlying proPlant expert allows the DSS to provide not only warnings of good migration conditions but also estimates of the progress of migration on the specific days it recommends for monitoring. When combined with the numbers of pollen beetles observed in field monitoring, this may give the user confidence to target decision‐making and control activities more effectively. For example, if there are two beetles per plant in a crop and migration is predicted to be 90% complete, the risk of any new migration breaching, say, a 5 beetles planta posteriori, using known weather data and known pollen beetle phenology. The validity of this approach was confirmed by the real‐time study, in which the reductions in the number of days of migration risk, forecast consultation and monitoring advised by the DSS compared with rule‐based advice matched or exceeded the reductions found a posteriori. Weather forecast data for both DSSs and for rule‐based advice should be chosen to reflect the conditions in the vicinity of the crop to which the advice is applied. proPlant expert aims to use a network of weather stations so that all crops are within 30 km of a station. Modern weather models enable modelling of forecast data at a grid scale finer than that of physical weather stations, enabling the interpolation of forecast data at a truly local scale. In this study, the average distance between weather stations and crops was 16 km. The two risk management tools performed well in spite of the inclusion of 11 sites more than 30 km from their weather stations, including one 80 km away.Most comparisons of the two systems presented here were made a posteriori assessment, as they predicted further into the future. However, they remained 85% or more accurate 2 days ahead. Modern weather forecasting models achieve high degrees of accuracy in predicting temperature, the basis of rule‐based advice on pollen beetle migration risk. At 45 sites across the United Kingdom in 2010–2012, 86.6% of maximum temperature forecasts were accurate to within ±2 °C on the second day of forecast . The degree of difference between proPlant expert's predictive advice in real time and its a posteriori advice at nine sites in 2011 was therefore consistent with the likely degree of inaccuracy in the weather forecasts driving proPlant's model.As expected, for both risk management tools, the accuracy with which they forecast good migration conditions moderately declined, relative to an In spring 2012, Bayer CropScience ran a trial version of proPlant expert on their UK website as part of their stewardship of insecticides, with positive feedback from a small sample of users.et al.A recent study on temperature–activity relationships in pollen beetles may provide scope to improve decision support models.et al.Temperature also influences the severity of bud damage when pollen beetles arrive on the crop. Ferguson For any DSS, reliability in offering accurate and effective timing of monitoring and control while minimising sampling effort and pesticide applications will remain key to engendering confidence among farmers and to encouraging them to adopt control thresholds more fully. A DSS based on a phenological model offers an approach to fulfil this role in pollen beetle management.Figure S1. Location of pollen beetle sampling sites used in this study.Click here for additional data file.Table S1. Comparison between migration indicators of the number of days elapsed between the date of first indication of migration and the first detection of a pollen beetle on traps or plants.Click here for additional data file.