Search

Clinical decision-support tools (DSTs) represent a valuable resource in healthcare. However, lack of Human Factors considerations and early design research has often limited their successful adoption. To complement previous technically focused work, we studied adoption opportunities of a future DST built on a predictive model of Alzheimer’s Disease (AD) progression. Our aim is two-fold: exploring adoption opportunities for DSTs in AD clinical care, and testing a novel combination of methods to support this process. We focused on understanding current clinical needs and practices, and the potential for such a tool to be integrated into the setting, prior to its development. Our user-centred approach was based on field observations and semi-structured interviews, analysed through workflow analysis, user profiles, and a design-reality gap model. The first two are common practice, whilst the latter provided added value in highlighting specific adoption needs. We identified the likely early adopters of the tool as being both psychiatrists and neurologists based in research-oriented clinical settings. We defined ten key requirements for the translation and adoption of DSTs for AD around IT, user, and contextual factors. Future works can use and build on these requirements to stand a greater chance to get adopted in the clinical setting.

This study assesses the diagnostic accuracy of ultrasound and magnetic resonance imaging (MRI) in diagnosing Stener lesions of the thumb. MEDLINE, PubMed, Embase and Cochrane CENTRAL were searched for studies using ultrasound or MRI to detect Stener lesions following suspected thumb ulnar collateral ligament injuries. The reference standard was surgical exploration or clinical joint stability. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A random-effects bivariate meta-analysis was used to estimate pooled sensitivity and specificity. Forest plots were generated. Nine ultrasound (315 thumbs) and six MRI (107 thumbs) studies were included in meta-analysis (all high risk of bias). Pooled sensitivity and specificity for ultrasound were 95% and 94%, and for MRI were 93% and 98%. Both ultrasound and MRI demonstrate high diagnostic accuracy in detecting Stener lesions. Ultrasound is an appropriate first-line imaging modality.

Objectives Intra-articular steroid injection is commonly used to treat base of thumb osteoarthritis (BTOA), despite a lack of large-scale data on safety and effectiveness. We estimate the incidence of serious complications and further procedures following BTOA injection, including the risk of post-operative serious surgical site infection for subsequent operative intervention. Methods Hospital Episode Statistics data linked to mortality records from 1 April 1998 to 31 March 2017 were used to identify all BTOA injections undertaken in adults in the National Health Service secondary care in England. Patients were followed up longitudinally until death or 31 March 2017. A multivariable regression with a Fine and Gray model adjusting for the competing risk of mortality in addition to age, sex and socioeconomic deprivation was used to identify factors associated with progression to further procedure. Secondary outcomes included serious complications after injection and subsequent surgical site infection. Results A total of 19 120 primary injections were performed during the 19-year period in 18 356 patients. Of these 76.5% were female; mean age 62 years (s.d. 10.6); 50.48% underwent further procedure; 22.40% underwent surgery. Median time to further intervention was 412 days (IQR 110–1945). Female sex was associated with increased risk of proceeding to surgery. Serious complication rate following injection was 0.04% (0.01–0.08) within 90 days. Of those proceeding to surgery 0.16% (0.06–0.34) presented with a wound infection within 30 days and 90 days, compared with an overall post-operative wound infection rate of 0.03% (0.02–0.05). Conclusions Very low rates of serious complications were identified following BTOA injections performed in secondary care; only one in five patients proceeded to subsequent surgery. Clinical trial registration clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03573765

Background The COVID-19 pandemic has exacerbated preexisting weaknesses in the global supply chain. Regional assessments by the Food and Drug Administration (FDA), European Medicines Agency (EMA), and independent consultants, have demonstrated various contributory causal factors requiring changes in policy, relationships, and incentives within the dynamic and developing networks. Human factors and ergonomics (HFE) is an approach that encourages sociotechnical systems thinking to optimize the performance of systems that involve human activity. The global supply chain can be considered such a system. However, it has neither been systematically examined from this perspective. Methods In 2015, the UK Chartered Institute of Ergonomics and Human Factors established the Pharmaceutical Sector Group. This unique group is open to all who work in the pharmaceutical sector at any level and in any discipline who share the vision of a pharmaceutical system that places an understanding of HFE at the heart of improving the use of healthcare products throughout their life cycles including their supply chains. Results For this complex system to work efficiently, it is paramount that we have effective coordination and integration between the different elements in the supply chain. HFE can give valuable insights and solutions for developing these complex social–technical systems effectively. Conclusion By partnering with international groups such as Biophorum and Bio Supply Chain Management Alliance, we wish to stimulate discussion about how sociotechnical thinking about HFE may help develop better monitoring and investigative techniques to strengthen global supply chains.

We performed Mendelian randomization analyses of body mass index and waist–hip ratio adjusted for body mass index in Dupuytren’s disease using summary statistics from genome-wide association study meta-analyses. We found that adiposity is causally protective against Dupuytren’s disease, with the inverse-variance weighted Mendelian randomization analysis estimating that a 1 standard deviation increase in body mass index (equivalent to 4.8 kg/m2) leads to 28% (95% confidence interval: 18–37%) lower relative odds of developing Dupuytren’s disease, and a 1 standard deviation increase in waist–hip ratio adjusted for body mass index (equivalent to a waist–hip ratio of 0.09) leads to 26% (95% confidence interval: 6–42%) lower relative odds of developing Dupuytren’s disease. We conclude from this study that regardless of the well-established negative health effects of obesity, the raised body mass index is associated with a lower risk of Dupuytren’s disease and may be causally protective for the development of the disease.

Progressive hand interphalangeal joint (IPJ) osteoarthritis is associated with pain, reduced function and impaired quality of life. However, the evidence surrounding risk factors for IPJ osteoarthritis progression is unclear. Identifying risk factors for IPJ osteoarthritis progression may inform preventative strategies and early interventions to improve long-term outcomes for individuals at risk of IPJ osteoarthritis progression. The objectives of the study were to describe methods used to measure the progression of IPJ osteoarthritis and identify risk factors for IPJ osteoarthritis progression. MEDLINE, EMBASE, Scopus, and The Cochrane Library were searched from inception to 19th February 2020 (PROSPERO CRD42019121034). Eligible studies assessed potential risk factor/s associated with IPJ osteoarthritis progression. Risk of bias was assessed using a modified QUIPS Tool, and a best evidence synthesis was performed. Of eight eligible studies, all measured osteoarthritis progression radiographically, and none considered symptoms. Eighteen potential risk factors were assessed. Diabetes (adjusted mean difference between 2.06 and 7.78), and larger finger epiphyseal index in males (regression coefficient β = 0.202) and females (β = 0.325) were identified as risk factors (limited evidence). Older age in men and women showed mixed results; 13 variables were not risk factors (all limited evidence). Patients with diabetes and larger finger epiphyseal index might be at higher risk of radiographic IPJ osteoarthritis progression, though evidence is limited and studies are biased. Studies assessing symptomatic IPJ osteoarthritis progression are lacking. Electronic supplementary material The online version of this article (10.1007/s00296-020-04687-1) contains supplementary material, which is available to authorized users.

Objectives: Errors in medication administration are common, with many interventions suggested to reduce them. For intravenous infusion–related errors, “smart infusion devices” incorporating dose error reduction software are widely advocated. Our aim was to explore the role of smart infusion devices in preventing or contributing to medication administration errors using retrospective review of 2 complementary data sets that collectively included a wide range of errors with different levels of actual or potential harm. Methods: We reviewed 216 medication administration errors identified from an observational study in clinical practice and 123 medication incidents involving infusion devices reported to a national reporting system. The impact of smart infusion devices in preventing or contributing to these errors was assessed by the research team and an expert panel. Results: The data suggest that use of any infusion device rather than gravitational administration may have prevented 13% of observed errors and 8% of reported incidents; additional reductions may be possible with standalone smart infusion devices, and further potential reductions with smart infusion devices integrated with electronic prescribing and barcode administration systems. An estimated 52% to 73% of errors that occurred with traditional infusion pumps could be prevented with such integrated smart infusion devices. In the few cases where smart infusion devices were used, these contributed to errors in 2 of 58 observed errors and 7 of 8 reported incidents. Conclusions: Smart infusion devices not only prevent some medication administration errors but can also contribute to them. Further evaluation of such systems is required to make recommendations for policy and practice.

Background Intravenous (IV) medication administration has traditionally been regarded to be error-prone with high potential for harm. A recent US multisite study revealed surprisingly few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error. Objectives To determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation in errors, discrepancies and practices, including the contribution of smart pumps. Design Phase 1 comprised an observational point-prevalence study of IV infusions, with debrief interviews and focus groups. Observers compared each infusion against the medication order and local policy. Deviations were classified as either errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs, and analytically in supplementary analyses. Phase 2 comprised in-depth observational studies at five of the participating sites to better understand causes of error and how safety is maintained. Workshops were held with key stakeholder groups, including health professionals and policy-makers, the public and industry. Setting Sixteen English NHS hospital trusts. Results Point-prevalence data were collected from 1326 patients and 2008 infusions. In total, 240 errors were observed in 231 infusions and 1489 discrepancies were observed in 1065 infusions. Twenty-three errors (1.1% of all infusions) were considered potentially harmful; one might have resulted in short-term patient harm had it not been intercepted, but none was judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of deviations varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or to respond to patient need. Smart pumps, as currently implemented, had little effect. Staff had developed practices to manage efficiency and safety pragmatically by working around systemic challenges. Limitations Local observers may have assessed errors differently across sites, although steps were taken to minimise differences through observer training, debriefs, and review and cleaning of data. Each in-depth study involved a single researcher, and these were limited in scale and scope. Conclusions Errors and discrepancies are common in everyday infusion administration but most have low potential for patient harm. Findings are best understood by viewing IV infusion administration as a complex adaptive system. Better understanding of performance variability to strategically manage risk may be more helpful for improving patient safety than striving to eliminate all deviations. Future work There is potential value in reviewing policy around IV infusion administration to reduce unnecessary variability, manage staff workload and engage patients, while retaining the principle that policy has to be fit for purpose, contextualised to the particular ward situation and treatment protocol, and sensitive to the risks of different medications. Further work on understanding infusion administration as a complex adaptive system might deliver new insights into managing patient safety. Funding This project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 7. See the NIHR Journals Library website for further project information.

BackgroundPatients often carry medication lists to mitigate information loss across healthcare settings. We aimed to identify mechanisms by which these lists could be used to support safety, key supporting features, and barriers and facilitators to their use.MethodsWe used a mixed-methods design comprising two focus groups with patients and carers, 16 semistructured interviews with healthcare professionals, 60 semistructured interviews with people carrying medication lists, a quantitative features analysis of tools available for patients to record their medicines and usability testing of four tools. Findings were triangulated using thematic analysis. Distributed cognition for teamwork models were used as sensitising concepts.ResultsWe identified a wide range of mechanisms through which carrying medication lists can improve medication safety. These included improving the accuracy of medicines reconciliation, allowing identification of potential drug interactions, facilitating communication about medicines, acting as an aide-mémoire to patients during appointments, allowing patients to check their medicines for errors and reminding patients to take and reorder their medicines. Different tools for recording medicines met different needs. Of 103 tools examined, none met the core needs of all users. A key barrier to use was lack of awareness by patients and carers that healthcare information systems can be fragmented, a key facilitator was encouragement from healthcare professionals.ConclusionOur findings suggest that patients and healthcare professionals perceive patient-held medication lists to have a wide variety of benefits. Interventions are needed to raise awareness of the potential role of these lists in enhancing patient safety. Such interventions should empower patients and carers to identify a method that suits them best from a range of options and avoid a ‘one size fits all’ approach.

Background Upper limb arthroplasty is an increasingly used treatment modality for end-stage joint disease of the shoulder, elbow and wrist. Whilst complications have been reported, the risk of venous thromboembolism has received less attention when compared to the lower limb. Guidance to aid clinical decision-making remains limited. This review aims to ascertain whether venous thromboembolism prophylaxis is beneficial after upper limb major joint replacement surgery. Methods A systematic review was performed in April 2019, utilising EMBASE, MEDLINE, Cochrane and Google Scholar. All clinical studies reporting venous thromboembolism incidence and risk reduction (after prophylaxis) in upper limb joint replacement were included. Results Twenty-four observational studies were identified. The reported incidence of venous thromboembolism ranged from 0.2% to 16% (weighted mean 0.68%) and 0.2% to 0.8% (weighted mean 0.49%) in shoulder and elbow arthroplasty, respectively. No records for wrist arthroplasty were found. In the literature, baseline venous thromboembolism risk of patients without an operation is reported as 0.5%. Discussion There is a lack of good quality evidence regarding the risks and benefits of venous thromboembolism prophylaxis in upper limb major joint replacement surgery. We recommend further research, ideally formal randomised controlled trials to guide recommendations. Although venous thromboembolism is rare in upper limb surgery, surgeons should remain vigilant to this possibility.

Background Hand osteoarthritis (OA) is a common condition, causing pain, stiffness and reduced quality of life. Incidence is higher amongst women, particularly around the age of the menopause. Whilst the relationship between sex hormones and OA has been studied in vitro, in epidemiological studies and in clinical trials of hormone replacement therapy (HRT), this study is the first to investigate the effect of estrogen-containing therapy on hand pain in post-menopausal women with symptomatic hand OA in a randomised study design. Methods This is a feasibility study of a double-blinded placebo-controlled intervention with 1:1 randomisation to either a combination of conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg (Duavive) or placebo. The target population is post-menopausal women with symptomatic hand OA, aiming to recruit 60–90 study participants. The primary objective is to assess the feasibility of a future fully powered randomised controlled trial (RCT). Participants will take the study medication for 24 weeks and be followed up for 28 weeks after randomisation. The primary outcomes used to determine feasibility are eligible participant identification rates and routes; recruitment, randomisation and retention rates of eligible participants; study medication compliance; and the likelihood of unintentional unblinding. Secondary outcomes include measures of hand pain, function, appearance and menopausal symptoms. An end of study questionnaire and focus groups will help to refine the final protocol for a full study. Discussion Identifying new treatments for symptomatic hand OA is a recognised research priority. The study will help us to understand whether there are sufficient interested and eligible individuals in this target population who would consider HRT for their hand symptoms. It will provide proof-of-concept RCT data on the effects of HRT on hand pain and other clinically relevant outcomes in this population. The study will gain valuable information on the feasibility of a full RCT and how best to run this. The findings will be published in a peer-reviewed journal and presented at a relevant conference. Trial registration ISRCTN12196200 registered on 15 January 2019.

Background The aim of this systematic review was to synthesise peer-reviewed literature assessing the impact of electronic prescribing (eP) systems on the working practices of healthcare professionals (HCPs) in the inpatient setting and identify implications for practice and research. Methods We searched PubMed, Medline, Embase, Cochrane and the Cumulative Index to Nursing Allied Health Literature databases for studies published from inception to November 2018. We included controlled, uncontrolled, observational and descriptive studies that explored the effect of eP on HCPs’ working practices in an inpatient setting. Data on setting, eP system and impact on working practices were extracted. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Emergent themes were identified and subjected to narrative synthesis. The protocol was registered with PROSPERO (registration CRD42017075804). Results Searches identified 1301 titles and abstracts after duplicate removal. 171 papers underwent full-text review. A total of 25 studies met the inclusion criteria, from nine different countries. Nineteen were of commercial eP systems. There were a range of study designs; most (n = 14) adopted quantitative methods such as cross-sectional surveys, ten adopted qualitative approaches and a further one used mixed methods. Fourteen of the 25 studies were deemed to be of high quality. Four key themes were identified: communication, time taken to complete tasks, clinical workflow, and workarounds. Within each theme, study findings differed as to whether the effects of eP on HCPs’ working practices were positive or negative. Conclusion There is a lack of consensus within the literature on the impact of eP on HCPs’ working practices. Future research should explore the strategies resulting in a positive impact on HCPs’ working practices and learn from those that have not been successful.

The brain signature and genetic basis of handedness are unclear. Wiberg et al. show that left-handers have higher functional connectivity between language networks, and identify four genomic regions associated with handedness. Variants within these regions appear, by influencing brain architecture, to predispose both to left-handedness and to certain neuropsychiatric diseases., Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging–handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in—or expression quantitative trait loci of—genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson’s, Alzheimer’s and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson’s disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness–imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases.

Secondary lymphedema is a common side effect of breast cancer treatment, with significant impact on patients' physical and psychological well-being. Conservative therapies are the gold standard treatment, however surgical options are becoming more popular. Lymphaticovenular anastomosis (LVA) is a supermicrosurgical procedure that aims to restore lymphatic flow by anastomosing damaged lymphatics to subcutaneous venules. We aimed to assess the effects of LVA on patients' limb volume and quality of life. Pre- and postoperative limb volumes and LYMQOL scores were collected for patients undergoing LVA for lymphedema secondary to breast cancer. Thirty-seven patients underwent LVA. A significant reduction was seen in median excess limb volume postoperatively (13.3%-6.6%, P < 0.005), with volumetric improvement seen in 78% of patients. Thirteen patients were able to discontinue compression garment use. Eighty-six percent of patients reported improved quality of life postoperatively with median LYMQOL score increasing from 90 to 104 points (P < 0.005). LVA is a minimally invasive surgical option for patients with early stage lymphedema. It can lead to significant volumetric improvements and in select patients, freedom from compression therapy. LVA can also lead to significant improvements in quality of life, in particular patients' mood and perception of their appearance.

Background: The administration of medication or fluids via the intravenous route is a common intervention for many hospital inpatients. However, little research has explored the safety and quality of intravenous therapy from the patient’s perspective, despite the role of the patient in patient safety receiving increased attention in recent years. Objective: To explore patients’ perspectives on the perceived quality and safety of intravenous infusions and identify implications for practice. Method: Qualitative semistructured interviews were conducted with 35 hospital patients receiving intravenous infusions in critical care, oncology day care, general medicine, and general surgery areas within 4 National Health Service hospitals in England. Data were analyzed thematically. Results: Four underlying and interlinked themes were identified: knowledge about intravenous infusions, challenges associated with receiving intravenous infusions, the role of health-care professionals, and patients’ attitudes toward receiving infusions. Conclusions: Patients were generally satisfied with receiving infusions; however, factors that contributed to decreased feelings of quality and safety were identified, suggesting areas for intervention. Issues to do with infusion pump alarms, reduced mobility, cannulation, and personal preferences for information, if given more attention, may improve patients’ experiences of receiving intravenous infusions.

ObjectivePrioritisation of important treatment uncertainties for ‘Common Conditions Affecting the Hand and Wrist’ via a UK-based James Lind Alliance Priority Setting Partnership.SettingThis process was funded by a national charitable organisation and based in the UK.ParticipantsAnyone with experience of common conditions affecting the adult hand and wrist, including patients, carers and healthcare professionals. All treatment modalities delivered by a hand specialist, including therapists, surgeons or other allied professionals, were considered.InterventionsEstablished James Lind Alliance Priority Setting Partnership methods were employed.Electronic and paper questionnaires identified potential uncertainties. These were subsequently confirmed using relevant, up-to-date systematic reviews. A final list of top 10 research uncertainties was developed via a face-to-face workshop with representation from patients and clinicians. Impact of research was sought by surveying hand clinicians electronically.Outcome measuresThe survey responses and prioritisation—both survey and workshop based.ResultsThere were 889 individually submitted questions from the initial survey, refined to 59 uncertainties across 32 themes. Eight additional uncertainties were added from published literature before prioritisation by 261 participants and the workshop allowed the final top 10 list to be finalised. The top 10 has so far contributed to the award of over £3.8 million of competitively awarded funding.ConclusionsThe Common Conditions in the Hand and Wrist Priority Setting Partnership identified important research questions and has allowed research funders to identify grant applications which are important to both patients and clinicians

Background: Several approaches to plate fixation of the proximal phalanx have been proposed, such as the dorsal extensor splitting approach and the lateral or dorso-lateral extensor sparing approach, which aims to minimise invasiveness to promote native extensor tendon glide. This study aimed to meta-analyse the outcomes of these two approaches. Methods: A systematic review of electronic databases was undertaken, and the outcomes of comparative studies meta-analysed. Results: Three studies were included for meta-analysis. Total active motion (TAM) was significantly greater in the extensor sparing group compared to the extensor splitting (Mean difference 8.52 degrees, 95%CI 0.8–16.36, p = 0.03). Conclusions: This study demonstrates that there is preliminary evidence favouring the use of extensor sparing approaches when fixing proximal phalanxes – however, this result requires validation with randomised controlled trials.

Radiographic osteoarthritis (OA) is most prevalent in the hand. The association of hand injury with pain or OA is unclear. The objective was to describe the relationship between hand injury and ipsilateral pain and OA in cricketers. Data from former and current cricketers aged ≥ 30 years was used. Data included history of cricket-related hand/finger injury leading to > 4 weeks of reduced exercise, hand/finger joint pain on most days of the last month, self-reported history of physician-diagnosed hand/finger OA. Logistic regression assessed the relationship between injury with hand pain (in former cricketers) and with OA (in all cricketers), adjusted for age, seasons played, playing standard. Of 1893 participants (844 former cricketers), 16.9% reported hand pain, 4.3% reported OA. A history of hand injury increased the odds of hand pain (OR (95% CI) 2.2, 1.4 to 3.6). A history of hand injury also had increased odds of hand OA (3.1, 2.1 to 4.7). Cricket-related hand injury was related to an increased odds of hand pain and OA. This highlights the importance of hand injury prevention strategies within cricket. The high prevalence of hand pain is concerning, and further research is needed to determine the impacts of hand pain.

Dupuytren’s disease (DD) is a common fibro-proliferative disorder of the palm. We estimated the risk of serious local and systemic complications and re-operation after DD surgery. We queried England’s Hospital Episode Statistics database and included all adult DD patients who were surgically treated. A longitudinal cohort study and self-controlled case series were conducted. Between 1 April 2007 and 31 March 2017, 121,488 adults underwent 158,119 operations for DD. The cumulative incidence of 90-day serious local complications was low at 1.2% (95% CI 1.1–1.2). However, the amputation rate for re-operation by limited fasciectomy following dermofasciectomy was 8%. 90-day systemic complications were also uncommon at 0.78% (95% CI 0.74–0.83), however operations routinely performed under general or regional anaesthesia carried an increased risk of serious systemic complications such as myocardial infarction. Re-operation was lower than previous reports (33.7% for percutaneous needle fasciotomy, 19.5% for limited fasciectomy, and 18.2% for dermofasciectomy). Overall, DD surgery performed in England was safe; however, re-operation by after dermofasciectomy carries a high risk of amputation. Furthermore, whilst serious systemic complications were unusual, the data suggest that high-risk patients should undergo treatment under local anaesthesia. These data will inform better shared decision-making regarding this common condition.

Proximal phalangeal fractures have traditionally been fixed via either Kirschner wires or dorsal plating. Concerns regarding lack of compression and potential for infection with wire fixation, and adhesion formation and stiffness with plating, have lead to alternative fixation methods, such as intramedullary screw fixation. However, the literature regarding this modality is limited. Methods: A systematic review was performed to review the literature regarding intramedullary screw fixation for proximal phalangeal fractures. English language studies that reported original data and commented on at least one postoperative measure of function were eligible for inclusion. 4 studies were eligible for inclusion, with a further 3 studies assessing proximal and middle phalanges analysed separately. Total active motion was greater than 240° in all proximal phalangeal studies; mean post-operative DASH was 3.62. 6% of patients sustained a major complication. Intramedullary screw fixation of proximal phalangeal fractures is safe, providing stable fixation to allow early motion.

Background Dupuytren's disease is a common complex disease caused by genetic and nongenetic factors. The role of many nongenetic risk factors is still unclear and debatable. This study aimed to systematically review the association between Dupuytren's disease and nongenetic risk factors. Methods A search strategy was developed based on the Population, Exposure, Comparison, Outcomes and Study framework. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted in MEDLINE, Embase, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to November of 2018. Title and abstract and then full-text screening against eligibility criteria was performed independently by two reviewers, and consensus was achieved by a third reviewer. The Effective Public Health Practice Project and the Oxford Centre for Evidence Based Medicine tools were used to assess study quality and to evaluate the level of evidence of included studies, respectively. Results Reviewers identified 4434 studies, of which 54 were included in the analysis. There was strong evidence for the association between Dupuytren's disease and advanced age, male sex, family history of Dupuytren's disease, and diabetes mellitus. Furthermore, heavy alcohol drinking, cigarette smoking, and manual work exposure showed a significant dose-response relationship. The quality of the included studies was mainly low or moderate, and most studies were level 3 or 4 on the Oxford Centre for Evidence Based Medicine scale. Conclusions The study results show a strong association between Dupuytren's disease and advanced age, male sex, family history of Dupuytren's disease, diabetes mellitus, heavy alcohol drinking, cigarette smoking, and manual work exposure. Further studies are required to explain the causal relationship of these associations.

Summary Background The prevalence of chronic wrist pain and subsequent functional decline is increasing. Diagnosis is challenging, with non-surgical treatment frequently failing. Recently, partial wrist denervation (PWD) has gained popularity as a procedure to alleviate chronic pain. Methods A systematic review was performed in April 2019. Inclusion criteria involved clinical studies with a minimum of ten wrists, focusing on PROMs, objective measures of function and complications. Papers investigating complete or mixed denervation procedures were excluded. Results Nine studies were included (292 wrists), all of which were observational in study design and limited in patient numbers, evaluation techniques and follow-up length. PWD appears to be associated with a reduction in pain, and functional improvement. Further surgery was required in 54 (24%) wrists at an average follow-up of 18 months. PWD was not found to complicate further surgery. Conclusion PWD is associated with improvement in short-term pain relief and functional status, yet carries a high re-operation rate without contraindicating further salvage surgery. Further research is required to evaluate the benefits, duration of relief and long-term complications of PWD.

Objective Radiographic hand OA affects one in five adults. Symptomatic hand OA can result in functional impairment, pain and reduced quality of life. A prevalent form of hand OA is IP joint OA, however prognostic factors for IP joint OA remain poorly understood. This systematic review aimed to identify prognostic factors for IP joint OA, and to summarize the diagnostic criteria for IP joint OA in prognostic studies. Methods EMBASE, MEDLINE, Scopus and The Cochrane Library were searched from inception until 19 February 2020 (PROSPERO CRD42019116782). Eligible studies described diagnostic criteria defining IP joint OA, and assessed potential prognostic factors for IP joint OA. Risk of bias was assessed using a modified Quality in Prognosis Studies (QUIPS) tool and a best evidence synthesis was used. Results Eighteen studies were included (risk of bias: eight high, three moderate, seven low). All defined OA radiographically, and three studies incorporated clinical symptoms into their definition of OA. Forty-nine potential prognostic factors were assessed. Eight were prognostic: older age in women, female gender (both moderate evidence); family history of Heberden’s nodes, Kashin–Beck disease, older age in men, dental occupation in men, finger fracture, parity (all limited evidence). Higher BMI in women (limited evidence) was prognostic for symptomatic radiographic OA. No prognostic factors for symptomatic OA were identified. Conclusion IP joint OA is most commonly defined radiographically, yet criteria were heterogeneous. Eight prognostic factors for radiographic IP joint OA and one for symptomatic radiographic IP joint OA were identified, all with limited or moderate evidence. Further studies on causality and on prognostic pathways are needed.

Lymphoedema is the accumulation of protein-rich interstitial fluid within subcutaneous tissue and skin as a result of dysfunction of the lymphatic system. It is an underestimated, widely neglected and debilitating chronic condition. This article presents an overview of lymphoedema and recent advances in its management.

Systems contradictions present challenges that need to be effectively managed, e.g. due to conflicting rules and advice, goal conflicts, and mismatches between demand and capacity. We apply FRAM (Functional Resonance Analysis Method) to intravenous infusion practices in an intensive care unit (ICU) to explore how tensions and contradictions are managed by people. A multi-disciplinary team including individuals from nursing, medical, pharmacy, safety, IT and human factors backgrounds contributed to this analysis. A FRAM model investigation resulting in seven functional areas are described. A tabular analysis highlights significant areas of performance variability, e.g. administering medication before a prescription, prioritising drugs, different degrees of double checking and using sites showing early signs of infection for intravenous access. Our FRAM analysis has been non-normative: performance variability is not necessarily wanted or unwanted, it is merely necessary where system contradictions cannot be easily resolved and so adaptive capacity is required to cope.

Carpal tunnel release provides an opportunity to study sensory nerve regeneration in humans. Schmid et al. show that cutaneous reinnervation correlates with symptom improvement after surgery. ADCYAP1 (encoding PACAP) expression is associated with sensory reinnervation in vivo and facilitates neuron outgrowth in vitro., We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P

Fibrotic disorders are some of the most devastating and poorly treated conditions in developed nations, yet effective therapeutics are not identified for many of them. A major barrier for the identification of targets and successful clinical translation is a limited understanding of the human fibrotic microenvironment. Here, we construct a stromal cell atlas of human fibrosis at single cell resolution from patients with Dupuytren’s disease, a localized fibrotic condition of the hand. A molecular taxonomy of the fibrotic milieu characterises functionally distinct stromal cell types and states, including a subset of immune regulatory ICAM1+ fibroblasts. In developing fibrosis, myofibroblasts exist along an activation continuum of phenotypically distinct populations. We also show that the tetraspanin CD82 regulates cell cycle progression and can be used as a cell surface marker of myofibroblasts. These findings have important implications for targeting core pathogenic drivers of human fibrosis. New anti-fibrotics aided by a better understanding of fibrotic cell subsets and their functions are needed. Here the authors perform single-cell RNA-seq and CyTOF on nodules from patients with Dupuytren’s disease to map subsets and the state of mesenchymal cells during pathogenic fibrogenesis.

This study aimed to determine if having an overweight or obese range body mass index (BMI) at time of beginning school is associated with increased fracture incidence in childhood. A dynamic cohort was created from children presenting for routine preschool primary care screening, collected in the Information System for Research in Primary Care (SIDIAP) platform in Catalonia, Spain. Data were collected from 296 primary care centers representing 74% of the regional pediatric population. A total of 466,997 children (48.6% female) with a validated weight and height measurement within routine health care screening at age 4 years (±6 months) between 2006 and 2013 were included, and followed up to the age of 15, migration out of region, death, or until December 31, 2016. BMI was calculated at age 4 years and classified using WHO growth tables, and fractures were identified using previously validated ICD10 codes in electronic primary care records, divided by anatomical location. Actuarial lifetables were used to calculate cumulative incidence. Cox regression was used to investigate the association of BMI category and fracture risk with adjustment for socioeconomic status, age, sex, and nationality. Median follow-up was 4.90 years (interquartile range [IQR] 2.50 to 7.61). Cumulative incidence of any fracture during childhood was 9.20% (95% confidence interval [CI] 3.79% to 14.61%) for underweight, 10.06% (9.82% to 10.29%) for normal weight, 11.28% (10.22% to 12.35%) for overweight children, and 13.05% (10.69% to 15.41%) for children with obesity. Compared with children of normal range weight, having an overweight and obese range BMI was associated with an excess risk of lower limb fracture (adjusted hazard ratio [HR] = 1.42 [1.26 to 1.59]; 1.74 [1.46 to 2.06], respectively) and upper limb fracture (adjusted HR = 1.10 [1.03 to 1.17]; 1.19 [1.07 to 1.31]). Overall, preschool children with an overweight or obese range BMI had increased incidence of upper and lower limb fractures in childhood compared with contemporaries of normal weight. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Mechanical force is a fundamental regulator of cell phenotype. Myofibroblasts are central mediators of fibrosis, a major unmet clinical need characterised by the deposition of excessive matrix proteins. Traction forces of myofibroblasts play a key role in remodelling the matrix and modulate the activities of embedded stromal cells. Here, we employ a combination of unsupervised computational analysis, cytoskeletal profiling and single cell traction force microscopy as a functional readout to uncover how the complex spatiotemporal dynamics and mechanics of living human myofibroblast shape sub-cellular profiling of traction forces in fibrosis. We resolve distinct biophysical communities of myofibroblasts, and our results provide a new paradigm for studying functional heterogeneity in human stromal cells., Summary: High resolution traction force microscopy at single-cell level reveals the biophysical landscape of primary human myofibroblasts.

Publisher's version (útgefin grein), Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods: We conducted genome-wide analyses across three independent studies and meta-analyzed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression, and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Measurements and Main Results: We identified and replicated threenewgenome-wide significant (P, R.J.A. is an Action for Pulmonary Fibrosis Research Fellow. L.V.W. holds a GSK/British Lung Foundation Chair in Respiratory Research. R.G.J. is supported by a National Institute for Health Research (NIHR) Research Professorship (NIHR reference RP-2017-08-ST2-014). I.N. is supported by the NHLBI (R01HL130796). B.G.-G. is funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (TESIS2015010057) cofunded by European Social Fund. J.M.O. is supported by the NHLBI (K23HL138190). C.F. is supported by the Spanish Ministry of Science, Innovation and Universities (grant RTC-2017-6471-1; Ministerio de Ciencia e Innovacion/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, Unión Europea) cofinanced by the European Regional Development Funds “A way of making Europe” from the European Union and by agreement OA17/008 with Instituto Tecnológico y de Energías Renovables to strengthen scientific and technological education, training, research, development and innovation in Genomics, Personalized Medicine and Biotechnology. The Spain Biobank array genotyping service was performed at CEGEN-PRB3-ISCIII, which is supported by PT17/0019, of the PE I+D+i 2013–2016, funded by Instituto de Salud Carlos III, and cofinanced by the European Regional Development Funds. P.L.M. is an Action for Pulmonary Fibrosis Research Fellow. M.O. is a fellow of the Parker B. Francis Foundation and a Scholar of the Michael Smith Foundation for Health Research. B.D.H. is supported by NIH K08 HL136928, Parker B. Francis Research Opportunity Award. M.H.C. and G.M.H. are supported by NHLBI grants R01HL113264 (M.H.C.), R01HL137927 (M.H.C.), R01HL135142 (M.H.C. and G.M.H.), R01111024 (G.M.H.), and R01130974 (G.M.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. T.M.M. is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017) and a British Lung Foundation Chair in Respiratory Research (C17-3). M.D.T. is supported by a Wellcome Trust Investigator Award (WT202849/Z/16/Z). The research was partially supported by the NIHR Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health. I.P.H. was partially supported by the NIHR Nottingham Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. I.S. is supported by Medical Research Council (G1000861) and Asthma UK (AUK-PG-2013-188). D.F. was supported by an Intermediate Fellowship from the Wellcome Trust (097152/Z/11/Z). This work was partially supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. V.N. is funded by an NIHR Clinical Lectureship. G.G. is supported by project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2016-023, A-2017-029, and A-2018-025. D.J.L. and A.M. are supported by Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SNP Health Association Resource (SHARe) project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and Massachusetts Institute of Technology (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0. This work was supported by NIH grants R01 HL131565 (A.M.), R01 HL103676 (D.J.L.), and R01 HL137234 (D.J.L.).

Summary What is known and objectives The use of enteral tube feeding at home is becoming more widespread, with patients ranging in age and diseases. Dysphagia and swallowing difficulties can compromise nutritional intake and the administration of oral medications, affecting therapeutic outcomes negatively. Carers’ experiences of medicines administration and medicines optimization have not been explored fully. The objectives of this study were to identify issues carers experience in medicines administration; the strategies they have developed to cope; and suggestions to improve the medicines administration process. Methods An online survey was promoted nationally; 42 carers completed it. Descriptive statistical analysis was applied, as well as thematic analysis of open‐ended responses. Results were compared against the 4 principles of medicines optimization. Results and discussion 93% of respondents administered medications with enteral feeding tubes, but only 62% had received advice from healthcare professionals and only 8% had received written information on how to do so. Responses identified 5 medicines administration issues experienced by carers; 4 strategies they developed to cope; and 3 main areas of suggestions to improve medicines administration via enteral feeding at home. What is new and conclusion The 4 principles of medicines optimization have not previously been applied to enteral feeding. We present a novel account of carers’ experiences, for example coping with ill‐suited formulations and a lack of training and support, which should inform better practice (Principle 1). Carers sometimes experience suboptimal choice of medicines (Principle 2). Carers’ practices are not always well‐informed and may affect therapeutic outcomes and safety (Principle 3). There is scope for improvement in carer training, education and support to better support medicines optimization (Principle 4)., Carers of patients using enteral tube feeding experience a variety of issues when administering medications, such as coping with ill‐suited formulations and a lack of training and support. Carers’ practices are not always well‐informed and may affect therapeutic outcomes and safety. There is scope for improvement in carer training, education and support to better support medicines optimization.

Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted., Kidney stones form in the presence of overabundance of crystal-forming substances such as Ca2+ and oxalate. Here, the authors report genome-wide association analyses for kidney stone disease, report seven previously unknown loci and find that some of these loci also associate with Ca2+ concentration and excretion.

It has been suggested that Dupuytren’s disease has an origin in Norse countries. We harnessed data from a genome-wide association study of Dupuytren’s disease and the People of the British Isles study to determine evidence for a Norse origin of Dupuytren’s disease. We computed Wright’s Fixation Index between Orkney (Norse ancestry), Wales (ancient British) and South East England (Anglo-Saxons); compared mean Wright’s Fixation Index in cases versus controls; used permutation to determine any excess of Norse inheritance in disease associated variants; constructed a genetic risk score for Dupuytren’s disease and applied this to the People of the British Isles dataset to look for systematic differences between counties with known high and low levels of Norse ancestry. Finally, chromosome painting was used to see whether Dupuytren’s disease-associated single nucleotide polymorphisms are geographically structured. In all analyses, no evidence was found for an excess of Norse ancestry in Dupuytren’s disease. We conclude that there is no genetic evidence for a ‘Viking origin of Dupuytren’s disease’.

Dupuytren’s disease is the common inherited tissue-specific fibrotic disorder. It’s characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia of the hand, with an onset typically in the sixth decade of life. Although genome-wide association studies (GWAS) have identified 24 genomic regions associated with Dupuytren’s risk, the biological mechanisms driving signal at these regions remain elusive. We identify potential biological mechanisms for Dupuytren’s disease by integrating the most recent, largest GWAS (ncases = 3,871, ncontrols = 4,686) with eQTLs (47 tissue panels from five consortia, total n = 3,975) to perform a transcriptome-wide association study (TWAS). We identify 43 tissue-specific gene associations with Dupuytren’s risk, one of which resides at least 0.5 Mb away from the 24 risk regions previously identified. We also estimate the genome-wide genetic correlation between Dupuytren’s disease and 45 complex traits and find significant genetic correlations between Dupuytren’s disease and body mass index (, P = 1.6 × 10−6), type II diabetes (, P = 1.7 × 10−4), triglycerides (, P = 3.5 × 10−4), and high-density lipoprotein (, P = 4.1 × 10−4), which suggests a shared genetic etiology. We further refine the genome-wide genetic correlation signal to identify 8 regions significantly negatively correlated with BMI and 3 regions significantly correlated (1 positively and 2 negatively correlated) with HDL; none of these regions contained the novel gene association identified by TWAS. Our results are consistent with previous epidemiological findings which show that lower BMI increases risk for Dupuytren’s disease. These 12 novel risk regions provide new insight into the biological mechanisms of Dupuytren’s disease and serve as a starting point for functional validation.

We only have a rudimentary understanding of the molecular and cellular determinants of human nerve regeneration. Here, we use carpal tunnel syndrome (CTS) as a human model system to prospectively evaluate correlates of neural regeneration and their relationship with clinical recovery after decompression surgery. At 6 months post-surgery, we noted a significant improvement of median nerve neurophysiological and somatosensory function. Serial skin biopsies revealed a partial recovery of intraepidermal innervation, whose extent correlated with symptom improvement. In myelinated afferents, nodal length increased postoperatively. Transcriptional profiling of the skin revealed 23 differentially expressed genes following decompression, with ADCYAP1 (encoding PACAP) being the most strongly upregulated and showing an association with regeneration of intraepidermal nerve fibres. Using human induced pluripotent stem cell-derived sensory neurons, we confirmed that PACAP significantly enhances axon outgrowth in vivo. Since PACAP signals through G-protein receptors, this pathway provides an interesting therapeutic target for human sensory nerve regeneration.

Supplemental Digital Content is available in the text., Background: Dupuytren’s disease is a common, chronic, fibroproliferative disease of the palmar fascia. The cause is unclear but includes genetic predisposition alongside environmental factors. Several studies have suggested an association between Dupuytren’s disease and excess mortality. The authors aimed to evaluate this association in adult patients in the United Kingdom and identify the causes of mortality. Methods: The authors used a large primary care database (Clinical Practice Research Datalink) linked to the Office of National Statistics to identify patients with Dupuytren’s disease between January 1, 1995, and December 31, 2013. Each patient was matched by age, sex, and general practitioner to five control patients without the disease. Cox regression models were used to study the association between Dupuytren’s disease and all-cause and cause-specific mortality, adjusting for confounders. Results: A total of 41,965 Dupuytren’s disease patients and 209,825 control patients were identified. The all-cause mortality rate was increased in both unadjusted (hazard ratio, 1.48; 99% CI, 1.29 to 1.70; p < 0.0001) and multivariable adjusted (hazard ratio, 1.43; 99% CI, 1.25 to 1.65; p < 0.0001) models in patients with Dupuytren’s disease, 12 years after diagnosis. Excess mortality was secondary to a wide range of causes, including cancer (hazard ratio, 1.66; 99% CI, 1.27 to 2.17; p < 0.0001), an effect that persisted after adjustment for confounders. Conclusions: There is excess mortality associated with Dupuytren’s disease that can be partially explained through environmental factors. From time of diagnosis in primary care, there is a 12-year window of opportunity for intervention to reduce the impact of these factors. The authors observed an increased risk of cancer mortality independent of confounders, and hypothesize a shared genetic risk between Dupuytren’s disease and cancer. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Background Deviations from local policy and national recommended best practice are common in the administration of intravenous infusions, but not all result in negative consequences. Some are the result of nurses’ clinical judgement. However, little is known about such practices and their effects on the safety of intravenous infusions. Our objective was to explore ways in which nurses contribute to system-level resilience when administering intravenous infusions. Methods We conducted a secondary analysis of qualitative data from debriefs and focus groups from a mixed methods study of errors and policy deviations in intravenous infusion administration across 16 English hospitals. Analysis focused on nurses’ contributions to system-level resilience, drawing on Larcos’s et al. framework of types of resilience. Results Five types of system-level resilience were identified in nurses’ behaviour: anticipatory resilience, responsive resilience, resilience based on past experience, workarounds and nurses performing informal ‘risk assessments’ in relation to how best to treat individual patients. Examples of practices contributing to infusion safety were found for each of these types of resilience. Conclusion Our findings suggest nurses are a key source of system-level resilience. Some behaviours that may be considered deviations from policy or best practice are the result of reasoned clinical judgement to improve infusion safety in response to the specific situation at hand. Adaptive behaviour is necessary to cope with the complexity of practice. There is a tension between standardisation and supporting flexibility in safety management.

RationaleIdiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. The mechanisms by which this arises are poorly understood and it is likely that multiple pathways are involved. The strongest genetic association with IPF is a variant in the promoter of MUC5B where each copy of the risk allele confers a five-fold risk of disease. However, genome-wide association studies have reported additional signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion.ObjectivesTo improve our understanding of mechanisms that increase IPF susceptibility by identifying previously unreported genetic associations.Methods and measurementsWe performed the largest genome-wide association study undertaken for IPF susceptibility with a discovery stage comprising up to 2,668 IPF cases and 8,591 controls with replication in an additional 1,467 IPF cases and 11,874 controls. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.Main resultsWe identified and replicated three new genome-wide significant (P-8) signals of association with IPF susceptibility (near KIF15, MAD1L1 and DEPTOR) and confirm associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF risk variants contribute to IPF susceptibility.ConclusionsNovel association signals support the importance of mTOR signalling in lung fibrosis and suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.

Many studies have highlighted the patient safety risks in intravenous medication administration, and various technological solutions have been proposed to mitigate those risks, including ‘smart pumps’ and closed-loop systems. Few studies describe these implementations in detail. In this article, we report on a sociotechnical investigation of a closed-loop documentation system linked with smart pumps for intravenous infusion administration on an intensive care unit. The smart pumps are ‘mapped’ to an electronic prescribing and medication administration system, allowing infusion rates, volumes and boluses of intravenous medication to be monitored in real time. Ethnographic observations were conducted over 37 h, including direct observation of infusion administration (n = 23 infusions), discussions with clinical staff and semi-structured interviews with intensive care unit managers (n = 2). Analysis was based on the Distributed Cognition for Teamwork (DiCoT) method to understand how information is processed across individuals, teams and technologies. We report on how the system works in context, and identify contributions and compromises to patient safety with new risks that need to be managed at bedside and intensive care unit level.

Objective As survival from cancer continues to improve, greater importance is placed on quality of life after surgery.Lymphoedemais a common and disabling complication of cancer treatment. Lymphaticovenularanastomosis(LVA) is a supermicrosurgical treatment option for lower limb lymphoedema. The aim of this study was to assess the effectiveness of LVA in reducing limb volume and its effect on quality of life of patients with secondary leg lymphoedema following treatment for cancer, includinggynaecological cancers. Methods Limb volume and patient rated quality of life were collected prospectively pre-operatively and at every post-operative appointment in this case series. All patients presenting to the clinic with stable or progressive leg lymphoedema despiteconservative therapywho were suitable candidates for LVA over a three-year period were included. Results Twenty-nine patients were treated with LVA, 19 for unilateral lymphoedema and 10 for bilateral. In unilateral cases median limb excess volume reduced from 27% to 16% post-operatively (pp Conclusions In selected patients with early stagelymphoedema secondaryto cancer treatment, LVA offers a minimally invasive surgical option that can achieve significant volumetric and quality of life improvements.

Background Breast cancer is the most common type of cancer amongst women worldwide, and one distressing complication of breast cancer treatment is breast and upper-limb lymphoedema. There is uncertainty regarding the effectiveness of surgical interventions in both the prevention and management of lymphoedema affecting the arm after breast cancer treatment. Objectives 1. To assess and compare the efficacy of surgical interventions for the prevention of the development of lymphoedema (LE) in the arm after breast cancer treatment. 2. To assess and compare the efficacy of surgical interventions for the treatment of established LE in the arm after breast cancer treatment. Search methods We searched the Cochrane Breast Cancer Group’s Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for all prospectively registered and ongoing trials on 2 November 2017. Reference lists of included studies were also handsearched by three review authors for additional eligible trials. Selection criteria All randomised controlled trials (RCTs) comparing a surgical intervention for the prevention or treatment of lymphoedema of the arm after breast cancer treatment to either standard intervention, placebo intervention, or another surgical intervention were included. Patients of both sexes and all ages who have had treatment for their breast cancer were considered. No limits were applied to language or study location. Three authors independently determined the eligibility of each study. Data collection and analysis Three authors independently extracted data for each included study using a pre-designed data extraction pro forma and used Cochrane's 'risk of bias' tool for assessing risk of bias. Dichotomous variables were analysed using the Mantel-Haenszel method to estimate risk ratios (RRs). Differences in continuous variables were expressed as mean differences (MDs). GRADE was used to assess the certainty of the evidence provided by the included studies. Main results Two studies involving 95 participants examined surgical interventions for preventing breast cancer-related lymphoedema. Both studies evaluated the efficacy of the lymphaticovenular anastomosis technique as part of a preventative management protocol. Both studies were deemed to be at unclear risk of bias overall. Statistical variation between the studies was low, which increases the reliability of the evidence. However, the two studies were conducted in the same centre. Lymphaticovenular anastomosis appears to result in a reduction in the incidence of lymphoedema compared to nonoperative management with a risk ratio of 0.20 (95% CI 0.06 to 0.63, P = 0.006; 95 participants; low-certainty evidence). The RCTs did not evaluate any of the secondary outcomes. One study involving 36 participants evaluated the effectiveness of vascularised lymph node transfer for treating breast cancer-related lymphoedema. The trial was deemed to be at unclear risk of bias. For participants suffering from stage 2 lymphoedema, the evidence suggested reductions in limb volume (MD -39.00%, 95% CI -47.37% to -30.63%, very low-certainty evidence), pain scores (MD -4.16, 95% CI -5.17 to -3.15, very low-certainty evidence), heaviness sensation (MD -4.27, 95% CI -5.74 to -2.80, very low-certainty evidence), mean number of infections/year (MD -1.22, 95% CI -2.00 to -0.44, very low-certainty evidence), and an improvement in overall function scores (MD -3.77, 95% CI -4.89 to -2.65, very low-certainty evidence) for those who had undergone vascularised lymph node transfer compared to those who had undergone no treatment. Authors' conclusions There is low-certainty evidence that lymphaticovenular anastomosis is effective in preventing the development of lymphoedema after breast cancer treatment based on the findings from two studies. One study providing very low-certainty evidence found that vascularised lymph node transfer is an efficacious option in the treatment of established stage 2 lymphoedema related to breast cancer. Important secondary outcomes in this review were rarely reported in the included studies. More high-quality RCTs are required to further elucidate the effectiveness of surgical interventions in the prevention and treatment of lymphoedema after breast cancer treatment. At the time of this review, no ongoing trials on this topic were identified.

ObjectivesTo provide accurate risk estimates of serious adverse events after elective shoulder replacement surgery for arthritis, including age and sex specific estimates of the lifetime risk of revision surgery.DesignPopulation based cohort study.SettingHospital episode statistics for NHS England, including civil registration mortality data.Participants58 054 elective shoulder replacements in 51 895 adults (aged ≥50 years) between April 1998 and April 2017.Main outcome measuresThe lifetime risk of revision surgery, calculated using an actuarial life table approach and the cumulative probability method. Rates of serious adverse events at 30 and 90 days post-surgery: pulmonary embolism, myocardial infarction, lower respiratory tract infection, acute kidney injury, urinary tract infection, cerebrovascular events, and all cause death. Secondary outcome measures were the number of surgeries performed each year and Kaplan-Meier estimates of revision risk at 3, 5, 10, and 15 years.ResultsThe number of shoulder replacements performed each year increased 5.6-fold between 1998 and 2017. Lifetime risks of revision surgery ranged from 1 in 37 (2.7%, 95% confidence interval 2.6% to 2.8%) in women aged 85 years and older to 1 in 4 (23.6%, 23.2% to 24.0%) in men aged 55-59 years. The risks of revision were highest during the first five years after surgery. The risk of any serious adverse event at 30 days post-surgery was 1 in 28 (3.5%, 3.4% to 3.7%), and at 90 days post-surgery was 1 in 22 (4.6%, 4.4% to 4.8%). At 30 days, the relative risk of pulmonary embolism compared with baseline population risk was 61 (95% confidence interval 50 to 73) for women aged 50-64. Serious adverse events were associated with increasing age, comorbidity, and male sex. 1 in 5 (21.2%, 17.9% to 25.1%) men aged 85 years and older experienced at least one serious adverse event within 90 days.ConclusionsYounger patients, particularly men, need to be aware of a higher likelihood of early failure of shoulder replacement and the need for further and more complex revision replacement surgery. All patients should be counselled about the risks of serious adverse events. These risks are higher than previously considered, and for some could outweigh any potential benefits. Our findings caution against unchecked expansion of shoulder replacement surgery in both younger and older patients. The more accurate age and sex specific estimates of risk from this study are long overdue and should improve shared decision making between patients and clinicians.Study registrationClinicalTrials.govNCT03573765.

BACKGROUND Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a multifactorial etiology and heritability of ~45-60%. To identify common genetic variants associated with nephrolithiasis we performed genome-wide association studies (GWAS) and meta-analysis in British and Japanese populations. METHODS GWAS and trans-ethnic meta-analysis of 12,123 kidney stone cases and 416,928 controls was performed. Genotype-phenotype correlations were established in a validation cohort of kidney stone patients. Biological pathways were studied in vitro in HEK293 cells. RESULTS Twenty loci associated with nephrolithiasis were identified, ten of which are novel. One such locus is associated with CYP24A1 and is predicted to affect vitamin D metabolism. Five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. The CYP24A1-associated locus, correlated with serum calcium concentration and number of kidney stone episodes in a validation cohort of nephrolithiasis patients. In addition, the DGKD-associated locus correlated with urinary calcium excretion in the validation cohort. Moreover, DGKD knockdown was shown to impair CaSR-signal transduction in vitro, an effect that was rectified by the calcimimetic cinacalcet, thereby supporting the role of DGKD in CaSR signaling. CONCLUSIONS Our study identified ten novel loci associated with kidney stone disease; six loci are predicted to influence calcium-sensing receptor and vitamin D metabolism pathways. These findings indicate that genotyping may help to inform risk of incident kidney stone disease prior to vitamin D supplementation and facilitate precision-medicine approaches, by targeting CaSR signaling or vitamin D activation pathways in patients with recurrent kidney stones.

Introduction Recurrent cellulitis is a frequent and challenging complication of lymphoedema. British Lymphology Society cellulitis guidelines state that decongestive lymphatic therapy reduces the frequency of cellulitis attacks, but do not mention the effect of surgical interventions. This systematic review aims to assess whether surgical interventions for lymphoedema reduce the frequency of attacks of cellulitis. Materials and methods Embase, Medline, and the Cochrane database were searched for relevant articles from database inception to January 2016. Four hundred and thirty-six abstracts were retrieved. Studies were included which contained quantitative data on cellulitis incidence before and after a surgical intervention. Two independent reviewers applied selection criteria, selecting 27 papers for full text review. Two were unavailable in the UK from any source. Results A variety of surgical techniques were utilized in the 25 papers included: lymphaticovenous anastomosis, superficial-to-deep lymphaticolymphatic anastomosis, lymph node transfer, Charles procedure, muscle flap transfer, Homan's procedure, and subcutaneous tissue excision below skin flaps. Five studies combined techniques. One study compared the intervention to a control group (physical therapy). Cellulitis incidence was decreased following surgical intervention in 24/25 studies included. Eight had quantifiable reductions in cellulitis over a set follow-up period; in the other 16 preoperative incidence was not precisely defined. Conclusion Surgery appears effective at reducing cellulitis incidence in lymphoedema. However, high quality evidence from randomized controlled trials is lacking. Future research should concentrate on comparison with control groups, for example compression alone versus compression with surgical intervention, in patients with lymphoedema and greater than two attacks of cellulitis per year.

Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.

IntroductionIntravenous medication administration has traditionally been regarded as error prone, with high potential for harm. A recent US multisite study revealed few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error.ObjectivesTo determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation, including the contribution of smart pumps.MethodsWe conducted an observational point prevalence study of intravenous infusions in 16 National Health Service hospital trusts. Observers compared each infusion against the medication order and local policy. Deviations were classified as errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs.ResultsData were collected from 1326 patients and 2008 infusions. Errors were observed in 231 infusions (11.5%, 95% CI 10.2% to 13.0%). Discrepancies were observed in 1065 infusions (53.0%, 95% CI 50.8% to 55.2%). Twenty-three errors (1.1% of all infusions) were considered potentially harmful; none were judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of errors and discrepancies varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or patient need. Smart pumps, as currently implemented, had little effect, with similar error rates observed in infusions delivered with and without a smart pump (10.3% vs 10.8%, p=0.8).ConclusionErrors and discrepancies are relatively common in everyday infusion administrations but most have low potential for patient harm. Better understanding of performance variability to strategically manage risk may be a more helpful tactic than striving to eliminate all deviations.

Introduction Risks of poor information transfer across health settings are well documented, particularly for medication. There is also increasing awareness of the importance of greater patient activation. Patients may use various types of patient-held information about medication (PHIMed) to facilitate medication transfer, which may be paper or electronic. However, it is not known how PHIMed should best be used, whether it improves patient outcomes, nor is its key ‘active ingredients’ known. Discussion with patients and carers has highlighted this as a priority for research. We aim to identify how PHIMed is used in practice, barriers and facilitators to its use and key features of PHIMed that support medicines optimisation in practice. Methods and analysis This study will take place in Greater London, England. We will include patients with long-term conditions, carers and healthcare professionals. The study has four work packages (WPs). WP1 involves qualitative interviews with healthcare professionals (n=16) and focus groups with patients and carers (n=20), including users and non-users of PHIMed, to study perceptions around its role, key features, barriers and facilitators, and any unintended consequences. WP2 will involve documentary analysis of how PHIMed is used, what is documented and read, and by whom, in a stratified sample of 60 PHIMed users. In WP3, we will carry out a descriptive analysis of PHIMed tools used/available, both electronic and paper, and categorise their design and key features based on those identified in WP1/2. Finally, in WP4, findings from WPs 1–3 will be integrated and analysed using distributed cognition as a theoretical framework to explore how information is recorded, transformed and propagated among different people and artefacts. Ethics and dissemination The study has National Health Service ethics approval. It will provide initial recommendations around the present use of PHIMed to optimise patient care for patients, carers and healthcare professionals.

Background Procedural and documentation deviations relating to intravenous (IV) infusion administration can have important safety consequences. However, research on such deviations is limited. To address this we investigated the prevalence of procedural and documentation deviations in IV infusion administration and explored variability in policy and practice across different hospital trusts. Methods We conducted a mixed methods study. This involved observations of deviations from local policy including quantitative and qualitative data, and focus groups with clinical staff to explore the causes and contexts of deviations. The observations were conducted across five clinical areas (general medicine, general surgery, critical care, paediatrics and oncology day care) in 16 National Health Service (NHS) trusts in England. All infusions being administered at the time of data collection were included. Deviation rates for procedural and documentation requirements were compared between trusts. Local data collectors and other relevant stakeholders attended focus groups at each trust. Policy details and reasons for deviations were discussed. Results At least one procedural or documentation deviation was observed in 961 of 2008 IV infusions (deviation rate 47.9%; 95% confidence interval 45.5–49.8%). Deviation rates at individual trusts ranged from 9.9 to 100% of infusions, with considerable variation in the prevalence of different types of deviation. Focus groups revealed lack of policy awareness, ambiguous policies, safety and practicality concerns, different organisational priorities, and wide variation in policies and practice relating to prescribing and administration of IV flushes and double-checking. Conclusions Deviation rates and procedural and documentation requirements varied considerably between hospital trusts. Our findings reveal areas where local policy and practice do not align. Some policies may be impractical and lack utility. We suggest clearer evidence-based standardisation and local procedures that are contextually practical to address these issues. Electronic supplementary material The online version of this article (10.1186/s12913-018-3025-x) contains supplementary material, which is available to authorized users.

A wide range of methods have been used to assess the potential clinical importance of medication errors, but it is neither clear which should be used, nor how they compare. In this paper, we compare two methods of assessment, using a dataset of errors identified in the administration of intravenous infusions in English hospitals, to inform future comparisons between studies. We assessed each of 155 errors identified in a study of intravenous infusion administration using two commonly used methods: an adapted form of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) method (an ordinal scale scored by local clinicians) and the Dean and Barber method (an interval scale ranging from 0 to 10 scored by a group of experts). We compared the two sets of scores using a scatter plot and calculated Spearman’s correlation coefficient. Using the NCC MERP method, 137 (88%) errors were rated C (‘an error occurred but was unlikely to cause harm despite reaching the patient’), 17 (11%) rated D (‘an error occurred that would be likely to have required increased monitoring’) and 1 (1%) rated E (‘an error occurred that would be likely to have caused temporary harm’). Errors ranged from 0 to 4.75 on the Dean and Barber scale with a mean of 1.7; 138 (89%) of errors were considered minor (scores of less than 3) and 17 (11%) as moderate (scores 3–7). Scores from the two methods were significantly but weakly correlated (correlation coefficient = 0.36, p =