Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older-Onset Multiple Sclerosis.

OBJECTIVE: Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group? METHODS: We used data from the UK MS Register to characterize demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years). RESULTS: In the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 28.3, p < 0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease-modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older-onset MS patients. INTERPRETATION: The more progressive nature of older-onset MS is associated with significant neurodegeneration, but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. ANN NEUROL 2024;95:471-486.

Epigenetic age estimation of wild mice using faecal samples.

Age is a key parameter in population ecology, with a myriad of biological processes changing with age as organisms develop in early life then later senesce. As age is often hard to accurately measure with non-lethal methods, epigenetic methods of age estimation (epigenetic clocks) have become a popular tool in animal ecology and are often developed or calibrated using captive animals of known age. However, studies typically rely on invasive blood or tissue samples, which limit their application in more sensitive or elusive species. Moreover, few studies have directly assessed how methylation patterns and epigenetic age estimates compare across environmental contexts (e.g. captive or laboratory-based vs. wild animals). Here, we built a targeted epigenetic clock from laboratory house mice (strain C57BL/6, Mus musculus) using DNA from non-invasive faecal samples, and then used it to estimate age in a population of wild mice (Mus musculus domesticus) of unknown age. This laboratory mouse-derived epigenetic clock accurately predicted adult wild mice to be older than juveniles and showed that wild mice typically increased in epigenetic age over time, but with wide variation in epigenetic ageing rate among individuals. Our results also suggested that, for a given body mass, wild mice had higher methylation across targeted CpG sites than laboratory mice (and consistently higher epigenetic age estimates as a result), even among the smallest, juvenile mice. This suggests wild and laboratory mice may display different CpG methylation levels from very early in life and indicates caution is needed when developing epigenetic clocks on laboratory animals and applying them in the wild.

Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

BACKGROUND: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease. AIM: To develop an algorithm to reliably identify MS cases within a national health data bank. METHOD: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry. RESULTS: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population. DISCUSSION: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS.

A common regulatory haplotype doubles lactoferrin concentration in milk.

BACKGROUND: Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental influences such as milking frequency, involution, or mastitis. A significant genetic influence has also been previously observed to regulate lactoferrin content in milk. Here, we conducted genetic mapping of lactoferrin protein concentration in conjunction with RNA-seq, ChIP-seq, and ATAC-seq data to pinpoint candidate causative variants that regulate lactoferrin concentrations in milk. RESULTS: We identified a highly-significant lactoferrin protein quantitative trait locus (pQTL), as well as a cis lactotransferrin (LTF) expression QTL (cis-eQTL) mapping to the LTF locus. Using ChIP-seq and ATAC-seq datasets representing lactating mammary tissue samples, we also report a number of regions where the openness of chromatin is under genetic influence. Several of these also show highly significant QTL with genetic signatures similar to those highlighted through pQTL and eQTL analysis. By performing correlation analysis between these QTL, we revealed an ATAC-seq peak in the putative promotor region of LTF, that highlights a set of 115 high-frequency variants that are potentially responsible for these effects. One of the 115 variants (rs110000337), which maps within the ATAC-seq peak, was predicted to alter binding sites of transcription factors known to be involved in lactation-related pathways. CONCLUSIONS: Here, we report a regulatory haplotype of 115 variants with conspicuously large impacts on milk lactoferrin concentration. These findings could enable the selection of animals for high-producing specialist herds.

Seasonal dynamics of the wild rodent faecal virome.

Viral discovery studies in wild animals often rely on cross-sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host-virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Utilizing noninvasive faecal samples from a long-term wild rodent study, we characterized viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis and Myodes glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most common virus families, Picornaviridae, show pronounced temporal changes in viral richness and evenness, which were associated with concurrent and up to ~3-month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks.

Experimental temperatures shape host microbiome diversity and composition.

Global climate change has led to more extreme thermal events. Plants and animals harbour diverse microbial communities, which may be vital for their physiological performance and help them survive stressful climatic conditions. The extent to which microbiome communities change in response to warming or cooling may be important for predicting host performance under global change. Using a meta-analysis of 1377 microbiomes from 43 terrestrial and aquatic species, we found a decrease in the amplicon sequence variant-level microbiome phylogenetic diversity and alteration of microbiome composition under both experimental warming and cooling. Microbiome beta dispersion was not affected by temperature changes. We showed that the host habitat and experimental factors affected microbiome diversity and composition more than host biological traits. In particular, aquatic organisms-especially in marine habitats-experienced a greater depletion in microbiome diversity under cold conditions, compared to terrestrial hosts. Exposure involving a sudden long and static temperature shift was associated with microbiome diversity loss, but this reduction was attenuated by prior-experimental lab acclimation or when a ramped regime (i.e., warming) was used. Microbial differential abundance and co-occurrence network analyses revealed several potential indicator bacterial classes for hosts in heated environments and on different biome levels. Overall, our findings improve our understanding on the impact of global temperature changes on animal and plant microbiome structures across a diverse range of habitats. The next step is to link these changes to measures of host fitness, as well as microbial community functions, to determine whether microbiomes can buffer some species against a more thermally variable and extreme world.

Collaborative evaluation of a pilot involvement opportunity: Cochrane Common Mental Disorders Voice of Experience College.

BACKGROUND: Involving consumers in systematic reviews can make them more valuable and help achieve goals around transparency. Systematic reviews are technically complex and training can be needed to enable consumers to engage with them fully. The Cochrane Common Mental Disorders group sought to engage people with lived experience of mental health problems in the Voice of Experience College, three workshops introducing them to systematic review methods and to opportunities to contribute as Cochrane consumers. We aimed to collectively evaluate the College from the perspective of both facilitators and consumers, to critically reflect on the experience, and to identify how the College could be sustained and spread to other review groups. METHODS: This study was a longitudinal qualitative and collaborative evaluation, structured around normalisation process theory. Both facilitators and consumers were involved in not only providing their perspectives but also reflecting on these together to identify key learning points. RESULTS: The workshops were positively evaluated as being engaging and supportive, largely due to the relational skills of the facilitators, and their willingness to engage in joint or two-way learning. The College suffered from a lack of clarity over the role of consumers after the College itself, with a need for greater communication to check assumptions and clarify expectations. This was not achieved due to pandemic disruptions, which nevertheless demonstrated that resources for involvement were not prioritised as core business during this period. CONCLUSIONS: Soft skills around communication and support are crucial to effective consumer engagement. Sustaining involvement requires sustained communication and opportunities to reflect together on opportunities and challenges. This requires committed resources to ensure involvement activity is prioritised. This is critical as negative experiences later in the involvement journey can undermine originally positive experiences if contributors are unclear as to what their involvement can lead to. Open discussions about this are necessary to avoid conflicting assumptions. The spread of the approach to other review groups could be achieved by flexibly adapting to group-specific resources and settings, but maintaining a core focus on collaborative relationships as the key mechanism of engagement. PATIENT AND PUBLIC CONTRIBUTION: Public contributors were collaborators throughout the evaluation process and have co-authored the paper.

Adapting a codesign process with young people to prioritize outcomes for a systematic review of interventions to prevent self-harm and suicide.

BACKGROUND: Research and clinical outcomes that matter to people with lived experience can significantly differ from those outcomes studied by researchers. To inform a future Cochrane review of suicide and self-harm prevention interventions, we aimed to work with young people with relevant lived experience to agree on priority outcomes. DESIGN: Four participatory codesign workshops were completed across two sites (New Zealand, United Kingdom) with 28 young people in total. We iteratively adapted the methods over the course of the study. RESULTS: 'Improved coping' and 'safer/more accepting environment to disclose' were the final top-rated outcomes. 'Reduction of self-harm' was considered a low priority as it could be misleading, stigmatizing and was considered a secondary consequence of other improvements. In contrast to typical research outcomes, young people emphasized the diversity of experience, the dynamic nature of improvement and holistic and asset-based framing. Methodologically, dialogue using design materials (personas) to thematically explore outcomes was effective in overcoming the initial challenge of disparate quantitative ratings. DISCUSSION: The results will directly inform the development of a Cochrane review, enabling identification of whether and how outcomes of most importance to young people are measured in trials. Rather than producing discrete measurable outcomes that could be easily added to the systematic review, the young people challenged the academic conceptualization of outcomes, with implications for future evidence synthesis and intervention research, and for future codesign. PATIENT OR PUBLIC CONTRIBUTION: Young people with lived experience were codesigners of the outcomes, and their feedback informed iterative changes to the study methods.

Contributors are representative, as long as they agree: How confirmation logic overrides effort to achieve synthesis in applied health research.

INTRODUCTION: The paradox of representation in public involvement in research is well recognized, whereby public contributors are seen as either too naïve to meaningfully contribute or too knowledgeable to represent 'the average patient'. Given the underlying assumption that expertise undermines contributions made, more expert contributors who have significant experience in research can be a primary target of criticism. We conducted a secondary analysis of a case of expert involvement and a case of lived experience, to examine how representation was discussed in each. METHODS: We analysed a case of a Lived Experience Advisory Panel (LEAP) chosen for direct personal experience of a topic and a case of an expert Patient and Public Involvement (PPI) panel. Secondary analysis was of multiple qualitative data sources, including interviews with the LEAP contributors and researchers, Panel evaluation data and documentary analysis of researcher reports of Panel impacts. Analysis was undertaken collaboratively by the author team of contributors and researchers. RESULTS: Data both from interviews with researchers and reported observations by the Panel indicated that representation was a concern for researchers in both cases. Consistent with previous research, this challenge was deployed in response to contributors requesting changes to researcher plans. However, we also observed that when contributor input could be used to support research activity, it was described unequivocally as representative of 'the patient view'. We describe this as researchers holding a confirmation logic. By contrast, contributor accounts enacted a synthesis logic, which emphasized multiplicity of viewpoints and active dialogue. These logics are incompatible in practice, with the confirmation logic constraining the potential for the synthesis logic to be achieved. CONCLUSION: Researchers tend to enact a confirmation logic that seeks a monophonic patient voice to legitimize decisions. Contributors are therefore limited in their ability to realize a synthesis logic that would actively blend different types of knowledge. These different logics hold different implications regarding representation, with the synthesis logic emphasizing diversity and negotiation, as opposed to the current system in which 'being representative' is a quality attributed to contributors by researchers. PATIENT OR PUBLIC CONTRIBUTION: Patient contributors are study coauthors, partners in analysis and reporting.

Participatory codesign of patient involvement in a Learning Health System: How can data-driven care be patient-driven care?

BACKGROUND: A Learning Health System (LHS) is a model of how routinely collected health data can be used to improve care, creating 'virtuous cycles' between data and improvement. This requires the active involvement of health service stakeholders, including patients themselves. However, to date, research has explored the acceptability of being 'data donors' rather than considering patients as active contributors. The study aimed to understand how patients should be actively involved in an LHS. DESIGN: Ten participatory codesign workshops were conducted with eight experienced public contributors using visual, collective and iterative methods. This led contributors to challenge and revise not only the idea of an LHS but also revise the study aims and outputs. RESULTS: The contributors proposed three exemplar roles for patients in patient-driven LHS, which aligned with the idea of three forms of transparency: informational, participatory and accountability. 'Epistemic injustice' was considered a useful concept to express the risks of an LHS that did not provide active roles to patients (testimonial injustice) and that neglected their experience through collecting data that did not reflect the complexity of their lives (hermeneutic injustice). DISCUSSION: Patient involvement in an LHS should be 'with and by' patients, not 'about or for'. This requires systems to actively work with and respond to patient feedback, as demonstrated within the study itself by the adaptive approach to responding to contributor questions, to work in partnership with patients to create a 'virtuous alliance' to achieve change. PATIENT OR PUBLIC CONTRIBUTION: Public contributors were active partners throughout, and co-authored the paper.

Trends in immediate breast reconstruction and radiation after mastectomy: A population study.

In the last decade, there has been an increase in women undergoing immediate breast reconstruction (IBR) at the time of mastectomy. Recent literature suggests a shift in practice: Surgeons are becoming more comfortable with IBR in the setting of possible postoperative adjuvant radiotherapy, despite the known complications. This study sought to investigate, at a population level, the patient and surgeon characteristics associated with the use of IBR and which of these factors were predictive of adjuvant radiotherapy. This retrospective population-based cohort study included all adult women who underwent mastectomy in the province of Ontario from 2007 to 2014. The Canadian Institute for Health Information (CIHI) administrative data base was used to generate patient demographic and clinical data. The Ontario Health Insurance Plan (OHIP) data base was used to elicit surgeon characteristics including clinical experience and volume of practice dedicated to breast surgery. Outcome variables included reconstruction concurrent with mastectomy, alloplastic vs autologous reconstruction, and use of radiation. A total of 25 861 patients underwent mastectomy and 2972 had IBR (11.5%). The rate of IBR after mastectomy increased over time from 7.2% in 2007 to 17.2% in 2014 (P < .001). There was also an increase in the proportion of patients with IBR who received radiation over the time period, from 19.4% in 2007 to 28.2% in 2014 (P = .003). In the first regression analysis, IBR was associated with younger patient age, residing in closer proximity to cancer clinics, absence of malignant breast disease (ie, prophylactic mastectomy), having a younger surgeon performing the mastectomy, and receiving care at a teaching hospital. A second analysis showed that patient variables predictive of radiation after IBR were a younger age and a more advanced cancer stage and no variables specific to surgeon or institution were predictive of radiation in patients with IBR. A significant increase in the rate of IBR as well as the use of radiation occurred over the 7-year study period. Multiple patient and surgeon factors were associated with IBR. Variables associated with radiation in IBR were harder to predict. Given the increase in the use of radiation in IBR, further research is needed to look at long-term outcomes in these patients at the population level.

Lost in the shadows: reflections on the dark side of co-production.

This article is a response to Oliver et al.'s Commentary 'The dark side of coproduction: do the costs outweigh the benefits for health research?' recently published in Health Research Policy and Systems (2019, 17:33). The original commentary raises some important questions about how and when to co-produce health research, including highlighting various professional costs to those involved. However, we identify four related limitations in their inquiry, as follows: (1) the adoption of a problematically expansive definition of co-production that fails to acknowledge key features that distinguish co-production from broader collaboration; (2) a strong focus on technocratic rationales for co-producing research and a relative neglect of democratic rationales; (3) the transposition of legitimate concerns relating to collaboration between researchers and practitioners onto work with patients, service users and marginalised citizens; and (4) the presentation of bad practice as an inherent flaw, or indeed 'dark side', of co-production without attending to the corrupting influence of contextual factors within academic research that facilitate and even promote such malpractice. The Commentary's limitations can be seen to reflect the contemporary use of the term 'co-production' more broadly. We describe this phenomenon as 'cobiquity' - an apparent appetite for participatory research practice and increased emphasis on partnership working, in combination with the related emergence of a plethora of 'co' words, promoting a conflation of meanings and practices from different collaborative traditions. This phenomenon commonly leads to a misappropriation of the term 'co-production'. Our main motivation is to address this imprecision and the detrimental impact it has on efforts to enable co-production with marginalised and disadvantaged groups. We conclude that Oliver et al. stray too close to 'the problem' of 'co-production' seeing only the dark side rather than what is casting the shadows. We warn against such a restricted view and argue for greater scrutiny of the structural factors that largely explain academia's failure to accommodate and promote the egalitarian and utilitarian potential of co-produced research.

An alternative to standard lumpectomy: a 5-year case series review of oncoplastic breast surgery outcomes in a Canadian setting

Background: Oncoplastic surgery (OPS) is becoming the new standard of care for breast-conserving surgery (BCS). It has become increasingly popular in Europe; however, it has not yet been widely accepted in North America. This study aims to describe the experience with OPS at a Canadian tertiary care centre. Methods: This study is a retrospective case series consisting of consecutive OPS cases at a single Canadian centre, the Royal Victoria Regional Health Centre in Barrie, Ontario, between 2009 and 2015. Results: A total of 275 women who consecutively underwent OPS were included. The average size of the tumour was 17 mm (standard deviation [SD] 13 mm; range 0­110 mm). The average specimen weight was 155 g (SD 146 g; range 15­1132 g). Invasive ductal carcinoma was the most common diagnosis (237 patients, 86.2%), followed by ductal carcinoma in situ (18 patients, 6.6%) and then invasive lobular carcinoma (15 patients, 5.5%). A positive margin was recorded in 37 (13.5%) patients. Immediate postoperative complications included seroma and edema (32.7%), wound infection (13.1%), hematoma (8.7%) and delayed wound healing (6.5%). A delay to adjuvant therapy due to postoperative complications occurred in 7 of 217 (3.2%) patients. The median follow-up was 18 months. There were local and distant recurrences in 9 (3.3%) and 2 (0.7%) patients, respectively. Overall survival was 99.3%. Conclusion: The findings of this study are comparable to results in the literature on OPS and demonstrate that OPS is an attractive alternative to standard lumpectomy for Canadian general surgeons who treat breast cancer.

Contexte: La chirurgie oncoplastique (COP) est en passe de devenir la nouvelle norme pour la chirurgie conservatrice du sein (CCS). Elle est de plus en plus populaire en Europe, mais elle n'a pas encore été largement adoptée en Amérique du Nord. Cette étude vise à décrire l'expérience d'un établissement de soins tertiaires au Canada en matière de COP. Méthodes: Cette étude repose sur une série rétrospective de cas de COP dans un établissement canadien, le Centre régional de santé Royal Victoria de Barrie, en Ontario, entre 2009 et 2015. Résultats: En tout, 275 cas consécutifs de COP ont été inclus. La taille moyenne des tumeurs était de 17 mm (écart-type [É.-T.] 13 mm; éventail 0­110 mm). Le poids moyen des spécimens était de 155 g (É.-T. 146 g; éventail 15­1132 g). Le diagnostic le plus fréquent était le carcinome canalaire invasif (237 patientes, 86,2 %), suivi du carcinome canalaire in situ (18 patientes, 6,6 %), puis du carcinome lobulaire invasif (15 patientes, 5,5 %). Une marge positive a été enregistrée chez 37 patientes (13,5 %). Parmi les complications postopératoires immédiates, mentionnons sérome et oedème (32,7 %), infection de plaie (13,1 %), hématome (8,7 %) et retard de cicatrisation de la plaie (6,5 %). Un retard du traitement adjuvant dû à des complications postopératoires est survenu chez 7 patientes sur 217 (3,2 %). Le suivi médian a été de 18 mois. On a noté des récurrences locales et à distance chez 9 (3,3 %) et 2 (0,7 %) patientes, respectivement. La survie globale a été de 99,3 %. Conclusion: Les conclusions de cette étude se comparent aux résultats recensés dans la littérature au sujet de la COP et démontrent que cette dernière est une solution de rechange attrayante à la tumorectomie standard pour les chirurgiens généraux qui soignent le cancer du sein au Canada.

Negative Pressure Wound Therapy Use to Decrease Surgical Nosocomial Events in Colorectal Resections (NEPTUNE): A Randomized Controlled Trial.

OBJECTIVE: Determine if negative pressure wound therapy (NPWT) reduces surgical site infection (SSI) in primarily closed incision after open and laparoscopic-converted colorectal surgery. BACKGROUND: SSIs after colorectal surgery are a common cause of morbidity. The prophylactic effect of NPWT has not been established. We undertook this study to evaluate if, among patients undergoing open colorectal resection, NPWT, as compared with standard postoperative dressings, is associated with a reduction in the rate of postoperative SSI. METHODS: In a randomized, controlled trial, 300 patients undergoing elective open colorectal surgery were assigned to receive prophylactic NPWT or standard gauze dressing. The primary end-point was 30-day SSI, as assessed by wound care experts blinded to treatment arm. Secondary outcomes included length of stay. Statistical analysis was performed on an intention-to-treat basis. A priori subgroup analysis was planned for patients who received a stoma at the time of initial operation. RESULTS: The incidence of SSI at 30-days postoperatively was no different between experimental and control groups (32% vs 34% respectively, P = 0.68). Length of stay was also no different at a median of 7 days (IQR 5) for both groups. Among patients receiving a stoma, there was also no difference in SSI between the experimental and control groups (38% vs 33% respectively, P = 0.66). CONCLUSIONS: Prophylactic use of NPWT on primarily closed incisions after open colorectal surgery was not associated with a decrease in SSI rate when compared with standard gauze dressing. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT02007018).

The Standardization of Outpatient Procedure (STOP) Narcotics: A Prospective Health Systems Intervention to Reduce Opioid Use in Ambulatory Breast Surgery.

BACKGROUND: During the past 15 years, opioid-related overdose death rates for women have increased 471%. Many surgeons provide opioid prescriptions well in excess of what patients actually use. This study assessed a health systems intervention to control pain adequately while reducing opioid prescriptions in ambulatory breast surgery. METHODS: This prospective non-inferiority study included women 18-75 years of age undergoing elective ambulatory general surgical breast procedures. Pre- and postintervention groups were compared, separated by implementation of a multi-pronged, opioid-sparing strategy consisting of patient education, health care provider education and perioperative multimodal analgesic strategies. The primary outcome was average pain during the first 7 postoperative days on a numeric rating scale of 0-10. The secondary outcomes included medication use and prescription renewals. RESULTS: The average pain during the first 7 postoperative days was non-inferior in the postintervention group despite a significant decrease in median oral morphine equivalents (OMEs) prescribed (2.0/10 [100 OMEs] pre-intervention vs 2.1/10 [50 OMEs] post-intervention; p = 0.40 [p < 0.001]). Only 39 (44%) of the 88 patients in the post-intervention group filled their rescue opioid prescription, and 8 (9%) of the 88 patients reported needing an opioid for additional pain not controlled with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) postoperatively. Prescription renewals did not change. CONCLUSION: A standardized pain care bundle was effective in minimizing and even eliminating opioid use after elective ambulatory breast surgery while adequately controlling postoperative pain. The Standardization of Outpatient Procedure Narcotics (STOP Narcotics) initiative decreases unnecessary and unused opioid medication and may decrease risk of persistent opioid use. This initiative provides a framework for future analgesia guidelines in ambulatory breast surgery.

Mastectomy flap necrosis after nipple-sparing mastectomy and immediate implant-based reconstruction: An evaluation of tumescence and sharp dissection technique on surgical outcomes.

Nipple-sparing mastectomy (NSM) with immediate implant-based reconstruction has better esthetic outcomes and improved patient satisfaction, in addition to being oncologically safe. A known complication of NSM is skin flap necrosis. The use of tumescence and sharp dissection may decrease this complication compared to the standard NSM technique using electrocautery. This is a retrospective review of patients who underwent a NSM between 2014 and 2017 at a regional cancer center. Tumescence with sharp dissection was compared to electrocautery. The primary outcome was skin flap necrosis. The secondary outcomes were operative time and management of the complication. A total of 62 patients underwent a NSM with 116 breasts being operated on. Full-thickness necrosis occurred more frequently in the standard electrocautery group (12.8%) compared to the tumescence and sharp dissection group (1.3%; P = 0.02). Partial-thickness necrosis also occurred more frequently in the standard group (33.3%) compared to the sharp dissection group (13.0%; P = 0.01). The operative time was significantly shorter in the sharp dissection group with the mean (SD) time being 183.5 (48.9) minutes compared to the standard electrocautery group at 202.9 (33.8) minutes (P = 0.03). NSM using tumescence and sharp dissection have a lower rate of the complications of partial- and full-thickness necrosis. Shorter operative time was also seen with the tumescent technique.

Referral of patients to diabetes prevention programmes from community campaigns and general practices: mixed-method evaluation using the RE-AIM framework and Normalisation Process Theory.

BACKGROUND: Each year around 5-10% of people with non-diabetic hyperglycaemia will develop type 2 diabetes mellitus. Diabetes prevention is a national and global public health concern. Diabetes Prevention Programmes, which seek to identify at-risk individuals and support entry to health improvement initiatives, recognise that enhanced identification and referral of at-risk individuals is required within primary care and beyond, through community-focused prevention approaches. We report an evaluation of a demonstrator site for the NHS Diabetes Prevention Programme in the UK, which piloted an enhanced Primary Care referral programme (sampling from patients identified as at-risk from general practice databases) and a Community identification programme (sampling from the general population through opportunistic identification in community locations) in an effort to maximise participation in prevention services. METHODS: We used mixed-methods evaluation to assess the impact of the two referral routes on participation in the Diabetes Prevention Programmes in line with the RE-AIM Framework (Reach, Effectiveness, Adoption, Implementation and Maintenance). Individual level patient data was descriptively analysed to assess identifications and eligible referrals made in each route. Semi-structured interviews conducted with referral staff and key stakeholders were analysed using thematic analysis and informed by Normalisation Process Theory. RESULTS: The nurse facilitated primary care referral route provided 88% of all referrals to the telephone DPP, compared to the community referral route which provided 5%, and the proportion joining the programme was higher among primary care referrals (45%) than community referrals (22%), and retention rates were higher (73% compared to 50%). The nurse-facilitated route integrated more easily into existing clinical processes. The community programme was impeded by a lack of collaborative inter-agency working which obscured the intended focus on high-risk populations despite conversion rates (numbers identified at risk who entered prevention programmes) being highest in areas of high deprivation. CONCLUSIONS: The study demonstrates the interaction of components, with effective Adoption and Implementation necessary to support Reach. The NPT analysis demonstrated the importance of consensus around not only the need for such programmes but agreement on how they can be delivered. Future programmes should support inter-agency communication and collaboration, and focus identification efforts on areas of high-risk.

A new measure to assess asthma's effect on quality of life from the patient's perspective.

BACKGROUND: The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the negative effect of asthma on quality of life (QoL) from the patient's perspective by using dimensions of Flanagan's Quality of Life Scale (QOLS), a measure of current QoL. OBJECTIVES: We sought to determine and compare the psychometric properties of the A-IQOLS and QOLS, including their sensitivities to differences and change in asthma status. METHODS: In a test-retest design (3- to 5-week interval) adults with persistent asthma underwent spirometry and were administered the A-IQOLS, other asthma outcome measures (Asthma Control Test, Asthma Symptom Utility Index, and the Marks and Juniper Asthma Quality of Life Questionnaires), and the QOLS. RESULTS: Participants' (n = 147) mean age was 49 years, 76% were white, 12% were Hispanic, and 65% were female. A-IQOLS and QOLS scores were significantly correlated with other asthma outcomes scores, except FEV1, but shared relatively low common variance with these measures. A-IQOLS but not QOLS score changes were significantly correlated with changes in asthma outcomes. An A-IQOLS standard error of measurement of 0.27 implies that a within-person score change of ±0.73 or greater constitutes a true change. The QOLS standard error of measurement was 0.43. CONCLUSIONS: A-IQOLS provides a reliable, valid, and unique assessment of the patient-perceived negative effect of asthma on QoL that is suitable for use in asthma clinical research and potentially in clinical care. Further studies are needed in diverse patient populations. QOLS, a measure of current QoL, is less sensitive to disease status changes but might be useful in characterizing study populations, in treatment adherence research, and as a clinical and research tool in patients with multiple, severe, and/or life-limiting chronic conditions.

Retrospective and Predictive Investigation of Fish Kill Events.

Fish kill investigations are critical to understanding threats to aquatic ecosystems and can serve as a measure of environmental disruption as well as an early indicator of emerging disease. The goal of this study was to analyze historical data related to such events among wild fish populations in Minnesota in order to assess the quality and completeness of the data and potential trends in fish kills. After excluding events with incomplete data (e.g., in which the location was not reported), we analyzed 225 unique fish kills from 2003 to 2013 that were recorded in two Minnesota Department of Natural Resources databases. The most reported fish kills occurred during 2007 (n = 41) and during the month of June (n = 81) across all years. Centrarchid species were present in the most fish kills (138), followed by cyprinid and ictalurid species, which were present in 53 and 40 events, respectively. Environmental factors were the most common cause of death reported. Models of environmental factors revealed that the maximum nighttime land surface temperature was the most critical factor in fish mortality, followed by changes in primary productivity and human disturbances. During the course of this study, data gaps were identified, including underreporting, inconsistent investigation, and the lack of definitive diagnoses, making interpretation of our results challenging. Even so, understanding these historical trends and data gaps can be useful in generating hypotheses and advancing data collection systems for investigating future fish kills. Our study is a primer investigation of fish kills providing information on the plausible areas, seasons, and fish groups at risk that can guide active environmental monitoring and epidemiological surveillance of fishes.