Complex wounds with exposed critical structures such as tendon and bone are a conundrum in wound management, especially in the setting where the patient is not a suitable candidate for flap surgery. While the individual use of negative pressure wound therapy (NPWT) and oxidised regenerated cellulose (ORC)/collagen/silver (PROMOGRAN PRISMA) dressing has been described in the literature, there are little data on the efficacy of their combined use. In this study, we describe a novel technique of combining the use of NPWT and ORC/collagen/silver dressings to manage complex wound beds as an alternative management option for patients not suitable for reconstructive flap surgery. This technique was performed in a series of 37 patients with complex lower‐extremity wounds that were not healing with conventional NPWT alone. All patients had open wounds with exposed critical structures that were difficult to manage, such as exposed tendon, bone, deep crevices, and joint. Successful coverage of exposed critical structures was achieved in 89% of patients, and coverage was achieved within 28 days of combination therapy in 82% of these patients, without any complications. The novel technique of combining ORC/collagen/silver dressing and NPWT provides a useful option in the armamentarium of a reconstructive surgeon dealing with difficult complex lower‐extremity wounds.
by Joseph Sweetman, George A. NewmanThe reduced importance of intent when judging purity (vs. harm) violations is some of the strongest evidence for distinct moral modules or systems: moral pluralism. However, research has indicated that some supposed differences between purity and harm moral domains are due to the relative weirdness of purity vignettes. This weirdness might lead to a failure to attend to or correctly process relevant mental state information. Such attentional failures could offer an alternative explanation (to separate moral systems) for the reduced exculpatory value of innocent intentions for purity violations. We tested if the different role of intent in each domain was moderated by individual differences in attentional efficiency, as measured by the Attention Network Task. If attentional efficiency explains the reduced exculpatory value of innocent intentions in purity (vs. harm) violations, then we would expect those high (vs. low) in attentional efficiency not to show the reduced exculpatory effect of innocent intentions in the purity (vs. harm) domain. Consistent with moral pluralism, results revealed no such moderation. Findings are discussed in relation to various ways of testing domain-general and domain-specific accounts of the mental state × domain effect, so that we might better understand the architecture of our moral minds.
by Costin Leu, Tom G. Richardson, Tobias Kaufmann, Dennis van der Meer, Ole A. Andreassen, Lars T. Westlye, Robyn M. Busch, George Davey Smith, Dennis LalEpilepsy is clinically heterogeneous, and neurological or psychiatric comorbidities are frequently observed in patients. It has not been tested whether common risk variants for generalized or focal epilepsy are enriched in people with other disorders or traits related to brain or cognitive function. Here, we perform two brain-focused phenome association studies of polygenic risk scores (PRS) for generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) with all binary brain or cognitive function-related traits available for 334,310 European-ancestry individuals of the UK Biobank. Higher GE-PRS were associated with not having a college or university degree (P = 3.00x10-4), five neuroticism-related personality traits (P-4), and having ever smoked (P = 1.27x10-6). Higher FE-PRS were associated with several measures of low educational attainment (P-5), one neuroticism-related personality trait (P = 2.33x10-4), having ever smoked (P = 1.71x10-4), and having experienced events of anxiety or depression (P = 2.83x10-4). GE- and FE-PRS had the same direction of effect for each of the associated traits. Genetic factors associated with GE or FE showed similar patterns of correlation with genetic factors associated with cortical morphology in a subset of the UKB with 16,612 individuals and T1 magnetic resonance imaging data. In summary, our results suggest that genetic factors associated with epilepsies may confer risk for other neurological and psychiatric disorders in a population sample not enriched for epilepsy.
To evaluate the impact of a nurse prescriber‐led protocol compared to a traditional physician‐led nonprotocol‐based approach had on maintaining targeted haemoglobin levels in patients on maintenance haemodialysis.
Anaemia is a common complication of chronic kidney disease and has a profound impact on the patients’ well‐being. Current practices place a greater emphasis on the decision‐making role of nurses in renal anaemia management. The introduction of nurse prescribing in this area is a relatively new concept.
A retrospective cohort design, covering an eight‐month period pre‐ and post introduction of a nurse prescriber‐led anaemia protocol; study adheres to the STROBE Statement.
Using a nonprobability convenience sample, data extracted from the medical records and electronic patient records system (eMed) related to 74 patients at a single outpatient haemodialysis centre located within an acute general teaching hospital. The primary outcome was patients’ haemoglobin level pre‐ and post introduction of the protocol. Secondary outcomes included erythropoietin‐stimulating agent and iron dosage, and serum ferritin and transferrin saturation levels.
There were no statistically significant differences between pre‐ and post protocol serum haemoglobin level and erythropoietin‐stimulating agent dosage. Under the management of the nurse prescriber, patients experienced a significant improvement in serum ferritin and transferrin saturation levels and required significantly less intravenous iron dosage.
This study, the first of its kind, found that patients receiving haemodialysis experience a significant improvement in iron indices while receiving a significantly lower amount of intravenous iron when managed by a nurse prescriber. Furthermore, the nurse prescribers’ decision‐making capacity is as effective as a physician‐led nonprotocol‐based approach in achieving haemoglobin target levels.
Nurse prescribers have a role in implementing a safe, standardised and sustained approach to anaemia management in outpatient haemodialysis settings without compromising patient care.
To evaluate the effectiveness of ‘first responder's care package’ on knowledge and skill on the management of road traffic accident (RTA) victims. The outcomes relate to the quality of first responder's care by autorickshaw drivers.
Autorickshaw drivers (N = 1,040) will be assessed to identify the impediments and knowledge to provide the first responder's care to RTA victims following which, 150 autorickshaw drivers will be selected based on a cut‐off knowledge score to train half of them using workshops. Drivers below 55 years and willing to participate will be recruited and drivers with serious health issues, homophobia and who cannot read English or Kannada will be excluded. Randomized controlled trial with repeated measures design will be adopted. Funding for the research is by the Indian Council of Medical Research and it is registered in the Clinical Trial Registry of India.
Road traffic accidents are responsible for 85% of the total global mortality and 90% of the ‘Disability Adjusted Life Years’ in the developing countries amounting to an annual loss of $65 billion to $100 billion. India's rate of RTA deaths is high and postcrash care is not addressed efficiently by any agencies in India. Autorickshaw drivers could be ideal candidates for teaching the first responder's care package in India as they are a constant presence on the roads and reach all the main roads and small lanes of the country.
The research will add to knowledge on quality of first responder's care provided to accident victims. If the intervention is found to be fruitful for the accident victims of the locality, it can be recommended to be implemented all over the state.
对自动驾驶汽车司机(N = 1,040)进行评估,确定为道路交通事故受害者提供急救员护理的障碍和知识,然后根据知识的临界得分选出150名自动驾驶汽车司机,对其中一半进行培训。招募55岁以下并愿意参与的司机,排除掉有严重健康问题、同性恋恐惧症和无法读懂英语或坎纳达语的司机。采用重复测量的随机对照试验设计。由印度医学研究委员会提供研究经费,并在印度临床试验注册处注册。
To decrease hospital length of stay in acute care surgery patients.
An observational cohort quality improvement project at a single tertiary referral centre.
A multidisciplinary team of physicians, nurses, case managers, and physical and occupational therapists was created to identify patients at risk for prolonged length of stay and implement weekly multidisciplinary rounding, with a systematic method of tracking progress in real time. The main outcome measure was hospital length of stay. The observed/expected ratios for length of stay 2 years before (2012–2014) and after (2014–2016) the intervention were compared.
A total of 6,120 patients was analysed. Early identification and action on barriers to discharge created a significant decrease in risk‐adjusted acute care surgery patient days per year (96 days) with limited added cost (1–2 hr per week). Patients discharged to home with or without services benefited most.
Decreasing length of stay in acute care surgery patients is possible without adding a significant burden to healthcare providers.
We describe a comprehensive, multidisciplinary initiative to decrease the length of stay of acute care surgery patients. Institutions can use existing resources in a sustainable manner to create a significant decrease in patient days per year with limited added cost.
by Nadia Diamond-Smith, George O. Onyango, Salome Wawire, George AyodoAn understanding of menstruation and its relationship to fertility can help women know the gestational age of any pregnancies, and thus identify preterm births. It can also help women avoid unintended pregnancies. However, little is known about women, and especially men’s, menstruation and fertility knowledge, outside of research on adolescent girls and stigma, and in low and middle income countries (LMIC). Additionally, little is known about practices surrounding the tracking of menstruation and fertility, and how, if at all, women would like to be supported in this. This research is the first phase in adapting a support tool for women in a LMIC, using an implementation science approach to understand relevant cultural needs. We explored women and men’s understanding of the relationship between menstruation and fertility, and their interest in support tools, through in-depth qualitative interviews in rural western Kenya. We interviewed 45 adult men, adult women and adolescent women all who had children in 2018. We found high levels of misinformation about menstruation and fertility, with most respondents not knowing the correct times when a woman could become pregnant. Common sources of knowledge included friends/family and school. Few women got information from health providers, even when they were at a facility already for care. There were mixed feelings from women about wanting support from male partners regarding tracking menstruation. While women were interested in a tool that could help them track their menstruation and pregnancies, they had privacy concerns about a mobile health app approach and preferred simpler calendar based tools. This study provides evidence for the high need for correct menstruation information among both men and women, and not only for adolescents. It also suggests that despite the international health community’s enthusiasm for mobile health solutions, that approach might not be most appropriate for this topic and setting.
by Jesse Elliott, Zemin Bai, Shu-Ching Hsieh, Shannon E. Kelly, Li Chen, Becky Skidmore, Said Yousef, Carine Zheng, David J. Stewart, George A. WellsBackground
We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC).Methods
We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046.Results
Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] –0.16 to 1.46; odds ratio 2.58 (0.76–11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39–0.54]; ceritinib 0.52 [0.42–0.64]; alectinib 300 BID 0.16 [0.08–0.33]; alectinib 600 BID 0.23 [0.17–0.30]; brigatinib 0.23 [0.15–0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17–0.70]; alectinib v. ceritinib 0.30 [0.14–0.64]; brigatinib v. crizotinib 0.49 [0.33–0.73]; brigatinib v. ceritinib 0.43 [0.27–0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39–0.83]) and crizotinib (0.68 [0.48–0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56–2.79]) and alectinib (1.60 [1.00–2.58]) but not ceritinib (1.25 [0.90–1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants.Conclusion(s)
Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
People in prison tend to experience poorer health, access to healthcare services and health outcomes than the general population. Use of video consultations (telemedicine) has been proven effective at improving the access, cost and quality of secondary care for prisoners in the USA and Australia. Implementation and use in English prison settings has been limited to date despite political drivers for change. We plan to research the implementation of a new prison-hospital telemedicine model in an English county to understand what factors drive or hinder implementation and whether the model can improve healthcare outcomes as demonstrated in other contextual settings.
We will undertake a hybrid type 2 implementation effectiveness study to gather evidence on both clinical and implementation outcomes. Data collection will be guided by the theoretical constructs of Normalisation Process Theory. We will prospectively collect data through: (1) prisoner/patient focus groups, interviews and questionnaires, (2) prison healthcare, hospital and wider prison staff interviews and questionnaires, (3) routine quality improvement and service evaluation data. Up to four prisons and three hospital settings in Surrey (England) will be included in the telemedicine research, dependent on their telemedicine readiness during the study period. Prisons proposed include male and female prisoners, remand (not yet sentenced) and sentenced individuals and different security categorisations. In addition, focus groups in five telemedicine naïve prisons will provide information on patient preconceptions and concerns surrounding telemedicine.
This study has received National Health Service Research Ethics Committee, Her Majesty’s Prison and Probation Service National Research Committee and Health Research Authority approval. Dissemination of results will take place through peer-reviewed journals, conferences and existing health and justice networks.
Autologous T-cells transduced to express a chimeric antigen receptor (CAR) directed against CD19 elicit high response rates in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). However, r/r B-NHL remissions are durable in fewer than half of recipients of second-generation CAR T-cells. Third-generation (3G) CARs employ two costimulatory domains, resulting in improved CAR T-cell efficacy in vitro and in animal models in vivo. This investigator-initiated, phase I dose escalation trial, termed ENABLE, will investigate the safety and preliminary efficacy of WZTL-002, comprising autologous T-cells expressing a 3G anti-CD19 CAR incorporating the intracellular signalling domains of CD28 and Toll-like receptor 2 (TLR2) for the treatment of r/r B-NHL.
Eligible participants will be adults with r/r B-NHL including diffuse large B-cell lymphoma and its variants, follicular lymphoma, transformed follicular lymphoma and mantle cell lymphoma. Participants must have satisfactory organ function, and lack other curative options. Autologous T-cells will be obtained by leukapheresis. Following WZTL-002 manufacture and product release, participants will receive lymphodepleting chemotherapy comprising intravenous fludarabine and cyclophosphamide. A single dose of WZTL-002 will be administered intravenously 2 days later. Targeted assessments for cytokine release syndrome and immune cell effector-associated neurotoxicity syndrome, graded by the American Society Transplantation and Cellular Therapy criteria, will be made. A modified 3+3 dose escalation scheme is planned starting at 5x104 CAR T-cells/kg with a maximum dose of 1x106 CAR T-cells/kg. The primary outcome of this trial is safety of WZTL-002. Secondary outcomes include feasibility of WZTL-002 manufacture and preliminary measures of efficacy.
Ethical approval for the study was granted by the New Zealand Health and Disability Ethics Committee (reference 19/STH/69) on 23 June 2019 for Protocol V.1.2. Trial results will be reported in a peer-reviewed journal, and results presented at scientific conferences or meetings.
One of the most severe complications in aesthetic and reconstructive surgeries is the partial or total necrosis of a skin flap. In our experimental study, we demonstrated the use of adipose‐derived stem cells in the increase of skin flap survival rates. Stem cells were isolated from the fat of Wistar rats and genetically modified to permanently produce a green fluorescent protein (GFP). Two random‐pattern skin flaps (2 cm × 8 cm) were elevated on the dorsal area of the spine, and after being separated from the surgical wounds with a thin silicone sheet, they were placed back onto their original location. Then, the autologous GFP‐producing cells were injected intradermally into the dorsal area of the rats. At the seventh day, after the implantation of the stem cells, a clinical and immunohistochemical control was performed. The fluorescence microscopy revealed green vascular formations, suggesting that autologous GFP stromal cells were converted into endothelial cells through neovascularization. In the control skin flaps, where no stromal cells were used, no fluorescence was observed. The statistical analysis showed significantly lower necrosis rates in the right‐sided flaps (i.e., the flaps where adipose‐derived stromal cells were injected) compared with the left‐sided ones. Findings from our study demonstrate that adipose‐derived stem cells play an important role in the improvement of skin flap survival. Neovascularization is an effective way of achieving it.
To identify how social return on investment (SROI) analysis—traditionally used by business consultants—has been interpreted, used and innovated by academics in the health and social care sector and to assess the quality of peer-reviewed SROI studies in this sector.
Community and residential settings.
A wide range of demographic groups and age groups.
The following databases were searched: Web of Science, Scopus, CINAHL, Econlit, Medline, PsychINFO, Embase, Emerald, Social Care Online and the National Institute for Health and Care Excellence. Limited uptake of SROI methodology by academics was found in the health and social care sector. From 868 papers screened, 8 studies met the criteria for inclusion in this systematic review. Study quality was found to be highly variable, ranging from 38% to 90% based on scores from a purpose-designed quality assessment tool. In general, relatively high consistency and clarity was observed in the reporting of the research question, reasons for using this methodology and justifying the need for the study. However, weaknesses were observed in other areas including justifying stakeholders, reporting sample sizes, undertaking sensitivity analysis and reporting unexpected or negative outcomes. Most papers cited links to additional materials to aid in reporting. There was little evidence that academics had innovated or advanced the methodology beyond that outlined in a much-cited SROI guide.
Academics have thus far been slow to adopt SROI methodology in the evaluation of health and social care interventions, and there is little evidence of innovation and development of the methodology. The word count requirements of peer-reviewed journals may make it difficult for authors to be fully transparent about the details of their studies, potentially impacting the quality of reporting in those studies published in these journals.
Closed incision negative pressure wound therapy (CINPWT) has been shown to be clinically effective compared with the traditional gauze dressing, reducing surgical site infections and wound complications. We evaluated the effect of CINPWT compared with gauze dressing on the need for revision surgery and survival after non‐traumatic major lower amputation. We included 309 patients undergoing 403 major lower amputations in a retrospective study from January 1, 2010 to November 23, 2017. A total of 139 patients received CINPWT, and 170 patients received stump bandage. There was no statistically significant difference between the two groups regarding the need for revision surgery (P = .45). Fourteen stump bandage patients and 15 CINPWT patients died in hospital (P = .57). One year after amputation, 55 CINPWT patients and 66 stump bandage patients had died (P = .82). Survival probabilities adjusted for age and gender 2 years after amputation were .52 (.43‐.61) and .49 (.42‐.58), respectively, and 3 years after amputation were .36 (.25‐.50) and .39 (.32‐.47), respectively. We also found no significant difference in the need for revision surgery in survival probabilities up till 3 years after amputation between patients treated with CINPWT and patients treated with gauze bandage postoperatively.
To determine the proportion of trials published in nursing science journals in 2017 that were prospectively registered.
A review of randomized controlled trials published in a Journal Citation Report nursing science journal in 2017.
Table of contents of included journals.
Randomized controlled trials were identified by manually reviewing the title of all papers published in included journals. Included trials were classified as: (a) Prospectively registered; (b) Retrospectively registered; (c) Registered but registration not reported in the manuscript; (d) Indeterminate registration; and (e) Not registered. Additionally, we recorded if the trial registration number was reported in the manuscript abstract.
Of 151 randomized controlled trials published in nursing science journals in 2017, 17 (11%) were prospectively registered. Thirty‐six (24%) trials were retrospectively and 93 (62%) not registered. We could not determine the registration status of five (3%) trials. The registration number was included in the abstract of two prospectively and eight retrospectively registered studies. Compared with the rest of the world, trial registration rates were significantly lower in Asian countries.
Two included trials were prospectively registered and reported a registration number in the abstract. Compared with other disciplines, rates of prospective trial registration are low. Nurse trialists must ensure that they prospectively register all trials.
We intended to replicate this review in subsequent years with a view to reporting improvements in prospective registration rates over time.
The treatment of chronic functional nausea or nausea due to functional dyspepsia in children is generally symptomatic. Moreover, these disorders pose a risk for worse psychosocial and health outcomes in children. Hypnotherapy (HT), by its ability to positively influence gastrointestinal and psychosocial functioning, may be an effective treatment for chronic nausea.
To test efficacy, this multicentre, parallel, randomised controlled, open label trial evaluates whether gut-directed HT is superior to standard medical treatment (SMT) for reducing nausea. The study will be conducted at eleven academic and non-academic hospitals across the Netherlands. A total of 100 children (8–18 years), fulfilling the Rome IV criteria for chronic idiopathic nausea or functional dyspepsia with prominent nausea, will be randomly allocated (1:1) to receive HT or SMT. Children allocated to the HT group will receive six sessions of HT during 3 months, while children allocated to the SMT group will receive six sessions of SMT+supportive therapy during the same period. The primary outcome will be the difference in the proportion of children with at least 50% reduction of nausea, compared with baseline at 12 months’ follow-up. Secondary outcomes include the changes in abdominal pain, dyspeptic symptoms, quality of life, anxiety, depression, school absences, parental absence of work, healthcare costs and adequate relief of symptoms, measured directly after treatment, 6 and 12 months’ follow-up. If HT proves effective for reducing nausea, it may become a new treatment strategy to treat children with chronic functional nausea or functional dyspepsia with prominent nausea.
Results of the study will be publicly disclosed to the public, without any restrictions, in peer-reviewed journal and international conferences. The study is approved by the Medical Research Ethics Committees United (MEC-U) in the Netherlands.
This study examines the role of age-disparate partnerships on young women’s HIV risk by investigating coital frequency and condom use within age-disparate partnerships involving women aged 15 to 24.
A community-based, cross-sectional study was conducted.
Participants were randomly selected using a two-stage random sampling method in uMgungundlovu district, KwaZulu-Natal, South Africa, between June 2014 and June 2015.
A total of 1306 15–24-year-old women in an ongoing heterosexual partnership were included in the analysis. Participants had to be a resident in the area for 12 months, and able to provide informed consent and speak one of the local languages (Zulu or English).
Sexual frequency was assessed by asking participants how many times they had sex with each partner in the past 12 months. The degree of condomless sex within partnerships was assessed in the survey by asking participants how often they used a condom with their partners.
Age-disparate partnerships were associated with a higher order category (once, 2–5, 6–10, 11–20, >20) of coital frequency (adjusted OR (aOR) 1.32, p
The finding that increased sexual activity is positively associated with age-disparate partnerships adds to the evidence that age-disparate partnerships pose greater HIV risk for young women. Our study results indicate that interventions to reduce risky sexual behaviour within age-disparate partnerships remain relevant to reducing the high HIV incidence rates among adolescent girls and young women.
Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory conditions, which result in significant morbidity worldwide. These conditions are associated with a range of non-specific symptoms, which in themselves are a target for health research. Such research is increasingly being conducted using electronic health records (EHRs), but computable phenotype definitions, in the form of code sets or code lists, are required to extract structured data from these large routine databases in a systematic and reproducible way. The aim of this protocol is to specify a systematic review to identify code sets for respiratory symptoms in EHRs research.
MEDLINE and Embase databases will be searched using terms relating to EHRs, respiratory symptoms and use of code sets. The search will cover all English-language studies in these databases between January 1990 and December 2017. Two reviewers will independently screen identified studies for inclusion, and key data will be extracted into a uniform table, facilitating cross-comparison of codes used. Disagreements between the reviewers will be adjudicated by a third reviewer. This protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines.
As a review of previously published studies, no ethical approval is required. The results of this review will be submitted to a peer-reviewed journal for publication and can be used in future research into respiratory symptoms that uses electronic healthcare databases.