by Conor Owens-Walton, David Jakabek, Brian D. Power, Mark Walterfang, Dennis Velakoulis, Danielle van Westen, Jeffrey C. L. Looi, Marnie Shaw, Oskar HanssonParkinson’s disease (PD) affects 2–3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry.
This study aims to evaluate the effects of a community‐based program entitled “Brain Vitality Enhancement (BRAVE)” on the cognitive function, physical and mental well‐being of persons with mild cognitive impairment.
This is a parallel wait‐list randomized controlled trial.
The BRAVE program consists of two phases. Phase 1 is an empowerment workshop for training 50 peer mentors to be the exercise ambassadors, while Phase 2 is a supervised exercise program for 250 persons with mild cognitive impairment. They will be randomly allocated to intervention or waitlist control groups. For the intervention group, the peer mentors and mentees will be matched according to gender and residential areas to form mentor‐mentee groups to attend an 8‐week supervised exercise training. The mentor‐mentee groups will continue to participate mentor‐directed exercise sessions in the community thereafter. A mobile application will be developed for self‐directed learning. We hypothesize that persons with mild cognitive impairment receiving the BRAVE program will demonstrate better cognitive function and health‐related quality of life than the control group who receive usual care. This study is funded by a grant from the Food and Health Bureau of the Government of Hong Kong Special Administrative Region in April 2018.
This study will empower a group of golden‐aged adults to be the ambassadors to promoting brain health in the community and persons with mild cognitive impairment to integrate moderate‐intensity exercise into their lifestyle to achieve long‐term beneficial effects on their cognition and well‐being.
Given the population with mild cognitive impairment is growing rapidly and expected to keep escalating in coming decades and limited treatment options for cognitive decline and its significant burden on the health and social care system, this study is timely to promote active aging in the society and reduce the burden associated with cognitive decline.
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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.
Millions of children die every year from serious childhood illnesses. Most deaths are avertable with access to quality care. Saving Children’s Lives (SCL) includes an abbreviated high-intensity training (SCL-aHIT) for providers who treat serious childhood illnesses. The objective of this study was to examine the impact of SCL-aHIT on knowledge acquisition and retention of providers.
76 participating centres who provide primary and secondary care in Kweneng District, Botswana.
Doctors and nurses expected by the District Health Management Team to provide initial care to seriously ill children, completed SCL-aHIT between January 2014 and December 2016, submitted demographic data, course characteristics and at least one knowledge assessment.
Retrospective, cohort study. Planned and actual primary outcome was adjusted acquisition (change in total knowledge score immediately after training) and retention (change in score at 1, 3 and 6 months), secondary outcomes were pneumonia and dehydration subscores. Descriptive statistics and linear mixed models with random intercept and slope were conducted. Relevant institutional review boards approved this study.
211 providers had data for analysis. Cohort was 91% nurses, 61% clinic/health postbased and 45% pretrained in Integrated Management of Childhood Illness (IMCI). A strong effect of SCL-aHIT was seen with knowledge acquisition (+24.56±1.94, p
aHIT for care of the seriously ill child significantly increased provider knowledge and loss of knowledge occurred over time. IMCI training did not significantly impact overall knowledge acquisition nor retention, while professional status impacted overall score and lost to follow-up impacted retention.
This study aims to evaluate the effects of a nurse‐coordinated, empowerment‐based integrated care model on self‐care behaviours and psychosocial outcomes in patients with atrial fibrillation and to explore how this intervention affects patients’ self‐care behaviours and quality of life.
This mixed‐methods study comprises a randomized controlled trial and an exploratory qualitative study.
A total of 392 community‐dwelling patients aged ≥65 years with a confirmed diagnosis of atrial fibrillation, a high stroke risk and no oral anticoagulants treatment will be recruited from the medical outpatient clinics of a university‐affiliated hospital. The patients will be randomly allocated to intervention or control groups, which will receive treatment via the nurse‐coordinated integrated care model or standard care, respectively. We hypothesize that compared with patients receiving standard care, atrial fibrillation patients exposed to the nurse‐coordinated care model will be more likely to achieve compatible patient and physician decisions regarding the use of oral anticoagulants, better changes in medication adherence, anxiety, depression and health‐related quality of life after the intervention. A subsample of 30 participants in the intervention group will also participate in a qualitative interview to provide their views and perceptions about the intervention. The ethical approval has obtained on 5 July 2018. This study is supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region on 29 June 2018.
This study will uniquely adopt an empowerment‐based approach to equip patients as active agents in atrial fibrillation management through a nurse‐coordinated integrated care model that comprehensively addresses their needs.
Patients with atrial fibrillation are currently receiving inadequate guideline‐recommended care. This study will address this important evidence‐practice gap by optimizing oral anticoagulant prescription and therapeutic effects and promotes effective patient self‐care, so as to achieve worldwide reductions in atrial fibrillation‐related morbidity, mortality, and healthcare burdens.
This study has been registered at ClinicalTrials.gov (NCT03924739).
This study aims to evaluate the effects of a 12‐week empowerment‐based self‐care programme on the cognitive, psychological and behavioural aspects of self‐care, health‐related quality of life and unplanned hospital service use of chronic heart failure patients and to estimate its cost‐effectiveness in reducing unplanned service use.
Randomized controlled trial with cost‐effectiveness analysis.
The study will recruit 236 community‐dwelling Chinese patients with chronic heart failure from regional hospitals in Hong Kong. Patients will be randomized in blocks to attend either the 12‐week empowerment‐based self‐care programme or a didactic education programme. Central to the empowerment‐based model is that the patients are the primary decision makers in self‐care and act autonomously to manage the disease. Collaborative approach and interactive teaching strategies are used to optimize patients' engagement and knowledge translation to real‐life practice. Outcome evaluation on self‐care maintenance and management, symptom perception, self‐care confidence, self‐care knowledge, health‐related quality of life and health service use will take place at baseline, on completion of the programme and at 12 weeks thereafter. Generalized estimating equations and Cox regression examine the intervention effects. Bootstrapping technique will be conducted to examine the cost‐effectiveness of the intervention. The study is formally funded in December 2016.
Chronic heart failure is associated with high level of hospital admissions, of which 40% is avoidable through effective self‐care. Although self‐care confidence is known to improve self‐care, no structured educative method has been developed to enhance this attribute. This study addresses this research gap with a stringent application of theory and research design.
The study illustrates the application of the empowerment model for self‐care enhancement in patients with chronic heart failure. The findings will inform the ways and values of this care model to enhance the disease management of this expanding clinical cohort.
To develop a culturally relevant conceptual map to discover perceptions of a statutory form of advance directive (AD) for Hong Kong Chinese.
This was the first study on AD using a concept mapping approach with two phases.
The data collection of the two phases was conducted from February 2016–February 2017. In Phase I, 96 participants were recruited using purposive sampling. In Phase II, multi‐dimensional scaling and hierarchical cluster analysis were used to create a concept map based on quantitative data.
The map depicted six clusters of factors affecting the acceptance of AD, with their importance rating in decreasing order: Conditional factor, value system, process of AD, physical and illness factor, personal situation factor, and socio‐cultural factor.
The study adopted a comprehensive approach to unfolding the multi‐faceted factors affecting the acceptance of ADs by stakeholders. Strategies targeting the clusters could be developed to facilitate the discussion and completion of AD.
(a) To explore the meanings of master's education in the professionalization of nursing; and (b) to describe the core attributes that nurses gained through master's study.
From June 2017 to June 2018, unstructured interviews were conducted with 12 master‐prepared nurses at advanced nursing position with minimum 5 years of postregistration experience. Collaborative thematic narrative analysis was conducted on verbatim transcripts. Members checking, peer validation and audience validation assured verisimilitude and utility.
There was a need to fit one's own assertion for professional growth in nursing career structure. Master's study equipped nurses with specialty skills and knowledge with enhanced reflexivity, which nurtured morality, problem‐solving ability and capacity to collaborate inter‐professionally. Master‐prepared nurses demonstrated effective clinical leadership through acting as change agents.
Master's level education and master‐prepared nurses are instrumental to the professionalization of nursing by expanding the roles of nurses. Nursing career mentoring will maximize nurses’ agency in healthcare system. Developing innovative inter‐professional pedagogy will nurture the reflexivity of master‐prepared nurses.
Human papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics).
The PAPCLEAR study is a single center longitudinal study following 150 women, aged 18–25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier.
This study has been approved by the Comité de Protection des Personnes Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/AR1612278, decision number DR-2016–488) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences.
Closed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes.
The trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and 16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated.
Cambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations.
by Yvonne J. Rosenberg, George K. Lewis, David C. Montefiori, Celia C. LaBranche, Mark G. Lewis, Lori A. Urban, Jonathan P. Lees, Lingjun Mao, Xiaoming JiangRecombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by the introduction of defined mutations in the crystallizable fragment (Fc) domains eg YTE (M252Y/S254T/T256E) and LS (M428L/N434S), as a consequence of increased half-lives and prolonged duration of protection. However, the functional properties of any biologic may be compromised by unanticipated immunogenicity in humans, rendering them ineffective. Several potent broadly neutralizing HIV monoclonal antibodies (bnAbs) have been identified that protect against SHIV challenge in macaque models and reduce HIV viremia in HIV-infected individuals. In the present study, the pharmacokinetics and immunogenicity of one or more 5mg/kg subcutaneous (SC) injections in naïve macaques of the HIV bnAb PGT121 and its PGT121-YTE mutant, both produced in plants, have been compared towards prolonging efficacy. Induction of anti-drug/anti-idiotypic antibodies (ADA, anti-id) has been monitored using both binding ELISAs and more functional inhibition of virus neutralization (ID50) assays. Timing of the anti-Id responses and their impact on pharmacokinetic profiles (clearance) and efficacy (protection) have also been assessed. The results indicate that ADA induction in naïve macaques may result both from injection of the previously non-immunogenic PGT121 into pre-primed animals and also by the introduction of the YTE mutation. Binding ADA antibody levels, induced in 7/10 macaques within two weeks of a first or second PGT121-YTE injection, were closely associated with both reduced pharmacokinetic profiles and loss of protection. However no correlation was observed with inhibitory ADA activity. These studies provide insights into both the structural features of bnAb and the immune status of the host which may contribute to the development of ADA in macaques and describe possible YTE-mediated changes in structure/orientation of HIV bnAbs that trigger such responses.
Exercise referral schemes (ERSs) are internationally widespread. This study aimed to gain an insight into differential engagement through understanding participant experiences of patients referred by healthcare professionals to one such scheme in the UK.
The study employed a qualitative longitudinal approach using semistructured interviews, with results reported using Consolidated criteria for Reporting Qualitative research guidelines.
Two leisure centres providing an ‘emerging best-practice’ ERS in northeast England.
Referred patients (n=11), who had not yet commenced the scheme, were recruited on a voluntary basis. Seven females and four males, with a range of non-communicable diseases, such as cardiovascular disease, mental health issues, diabetes, overweight/obesity and musculoskeletal problems, participated.
24-weeks, two times per week, of supervised exercise sessions and three one-to-one assessments (prescheme, 12 weeks and 24 weeks) for patients referred from primary and secondary care.
Two longitudinal semistructured interviews, prior to commencement and 12–20 weeks later, were thematically analysed using the framework approach. Analysis comprised seven stages: transcription, familiarisation, coding, development and application of an analytical framework, charting data using a matrix and interpretation of data. Interpretation went beyond descriptions of individual cases to develop themes, which identified and offered possible explanations for differing participant experiences.
Three overarching themes emerged. First, ‘success’, with engaged participants focused on health outcomes and reported increases in physical activity. Second, ‘struggle’, with short-term success but concerns regarding continued engagement. Participants reported scheme dependency and cyclical needs. Finally, ‘defeat’, where ill health, social anxiety and/or poor participation experience made engagement difficult.
Some success in engaging those with non-communicable diseases was reported, resulting in positive effects on health and well-being. The study highlights complexity within ERSs and inequality of access for those with challenging health and social circumstances. Improved, or different, behaviour change support is required for referrals finding engagement difficult.
To characterise how online media coverage of journal articles on cancer funded by the US government varies by cancer type and stage of the cancer control continuum and to compare the disease prevalence rates with the amount of funded research published for each cancer type and with the amount of media attention each receives.
A cross-sectional study.
The United States.
The subject of analysis was 11 436 journal articles on cancer funded by the US government published in 2016. These articles were identified via PubMed and characterised as receiving online media attention based on data provided by Altmetric.
16.8% (n=1925) of articles published on US government-funded research were covered in the media. Published journal articles addressed all common cancers. Frequency of journal articles differed substantially across the common cancers, with breast cancer (n=1284), lung cancer (n=630) and prostate cancer (n=586) being the subject of the most journal articles. Roughly one-fifth to one-fourth of journal articles within each cancer category received online media attention. Media mentions were disproportionate to actual burden of each cancer type (ie, incidence and mortality), with breast cancer articles receiving the most media mentions. Scientific articles also covered the stages of the cancer continuum to varying degrees. Across the 13 most common cancer types, 4.4% (n=206) of articles focused on prevention and control, 11.7% (n=550) on diagnosis and 10.7% (n=502) on therapy.
Findings revealed a mismatch between prevalent cancers and cancers highlighted in online media. Further, journal articles on cancer control and prevention received less media attention than other cancer continuum stages. Media mentions were not proportional to actual public cancer burden nor volume of scientific publications in each cancer category. Results highlight a need for continued research on the role of media, especially online media, in research dissemination.
Surgical site infection (SSI) complicates 5% of all surgical procedures in the UK and is a major cause of postoperative morbidity and a substantial drain on healthcare resources. Little is known about the incidence of SSI and its consequences in women undergoing surgery for gynaecological cancer. Our aim was to perform the first national audit of SSI following gynaecological cancer surgery through the establishment of a UK-wide trainee-led research network.
In a prospective audit, we collected data from all women undergoing laparotomy for suspected gynaecological cancer at 12 specialist oncology centres in the UK during an 8-week period in 2015. Clinicopathological data were collected, and wound complications and their sequelae were recorded during the 30 days following surgery.
In total, 339 women underwent laparotomy for suspected gynaecological cancer during the study period. A clinical diagnosis of SSI was made in 54 (16%) women. 33% (18/54) of women with SSI had prolonged hospital stays, and 11/37 (29%) had their adjuvant treatment delayed or cancelled. Multivariate analysis found body mass index (BMI) was the strongest risk factor for SSI (OR 1.08[95% CI 1.03 to 1.14] per 1 kg/m2 increase in BMI [p=0.001]). Wound drains (OR 2.92[95% CI 1.41 to 6.04], p=0.004) and staple closure (OR 3.13[95% CI 1.50 to 6.56], p=0.002) were also associated with increased risk of SSI.
SSI is common in women undergoing surgery for gynaecological cancer leading to delays in discharge and adjuvant treatment. Resultant delays in adjuvant treatment may impact cancer-specific survival rates. Modifiable factors, such as choice of wound closure material, offer opportunities for reducing SSI and reducing morbidity in these women. There is a clear need for new trials in SSI prevention in this patient group; our trainee-led initiative provides a platform for their successful completion.
To compare two different models of public oral health in primary care services, a so-called family health strategy (FHS), as opposed to non-FHS services designated as ‘conventional’ healthcare (CHC), regarding the presence and extent of the attributes of ‘good’ primary healthcare (PHC). The null hypothesis of this study is that the attributes do not differ between the FHS and CHC.
Public PHC services in Curitiba, the state capital of Paraná.
PHC users of the public oral health network (n=900) and dentists active in this municipal network (n=203).
The Primary Care Assessment Tool (PCATool)-Dentists and PCATool-Users were used to analyse the primary outcomes (‘essential’ attributes) and secondary outcomes (‘derived’ attributes) in the PHC.
Overall, the primary care services in oral health were well evaluated, both by users and by dentists, with mean scores ascribed to PHC attributes mostly above the cut-off point (6.6). The exception for users were affiliation (6.36; 95% CI 6.11 to 6.60) and accessibility (5.83; 95% CI 5.78 to 5.89); and for dentists the accessibility (5.80; 95% CI 5.63 to 5.96). When comparing FHS and CHC, there was a superiority of the FHS model, which reached a general mean score of 7.53 (95% CI 7.48 to 7.58) among users and 7.56 (95% CI 7.45 to 7.67) among dentists; on the other hand, the CHC general mean score was of 6.61 (95% CI 6.49 to 6.73) and 6.68 (95% CI 6.56 to 6.80) respectively for users and dentists.
The results reveal a reasonable level of attainment of PHC attributes in the services investigated. Nevertheless, public health managers should make efforts to reduce the difficulties faced by users in accessing dental care. The more positive results achieved by FHS services indicate that the provision of oral healthcare under this strategy should be expanded.
Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.
This parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.
The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).
The findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).
Atrial fibrillation (AF) is one of the leading causes of cerebrovascular mortality and morbidity. Oral anticoagulants (OACs) have been shown to reduce the incidence of cardioembolic stroke in patients with AF, adherence to treatment being an essential element for their effectiveness. Since the release of the first non-vitamin K antagonist oral anticoagulant, several observational studies have been carried out to estimate OAC adherence in the real world using pharmacy claim databases or AF registers. This systematic review aims to describe secondary adherence to OACs, to compare adherence between OACs and to analyse potential biases in OAC secondary adherence studies using databases.
We searched on PubMed, SCOPUS and Web of Science databases (completed in 26 September 2018) to identify longitudinal observational studies reporting days’ supply adherence measures with OAC in patients with AF from refill databases or AF registers. The main study endpoint will be the percentage of patients exceeding the 80% threshold in proportion of days covered or the medication possession ratio. Two reviewers will independently screen potential studies and will extract data in a structured format. A random-effects meta-analysis will be carried out to pool study estimates. The risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies and we will also assess some study characteristics that could affect days’ supply adherence estimates.
This systematic review using published aggregated data does not require ethics approval according to Spanish law and international regulations. The final results will be published in a peer-review journal and different social stakeholders, non-academic audiences and patients will be incorporated into the diffusion activities.
by Valentine U. Chukwuma, Nurgun Kose, D. Noah Sather, Gopal Sapparapu, Rachel Falk, Hannah King, Vidisha Singh, Rebecca Lampley, Delphine C. Malherbe, Noah T. Ditto, Jonathan T. Sullivan, Trevor Barnes, Benjamin J. Doranz, Celia C. Labranche, David C. Montefiori, Spyros A. Kalams, Nancy L. Haigwood, James E. Crowe Jr.Broadly neutralizing antibodies (bNAbs) are rarely elicited by current human immunodeficiency virus type 1 (HIV-1) vaccine designs, but the presence of bNAbs in naturally infected individuals may be associated with high plasma viral loads, suggesting that the magnitude, duration, and diversity of viral exposure may contribute to the development of bNAbs. Here, we report the isolation and characterization of a panel of human monoclonal antibodies (mAbs) from two subjects who developed broadly neutralizing autologous antibody responses during HIV-1 infection. In both subjects, we identified collections of mAbs that exhibited specificity only to a few autologous envelopes (Envs), with some mAbs exhibiting specificity only to a subset of Envs within the quasispecies of a particular sample at one time point. Neutralizing antibodies (NAbs) isolated from these subjects mapped mostly to epitopes in the Env V3 loop region and the CD4 binding site. None of the individual neutralizing mAbs recovered exhibited the cumulative breadth of neutralization present in the serum of the subjects. Surprisingly, however, the activity of polyclonal mixtures comprising individual mAbs that each possessed limited neutralizing activity, could achieve increased breadth of neutralizing activity against autologous isolates. While a single broadly neutralizing antibody targeting one epitope can mediate neutralization breadth, the findings presented here suggest that a cooperative polyclonal process mediated by diverse antibodies with more limited breadth targeting multiple epitopes also can achieve neutralization breadth against HIV-1.
Unlike other forms of evaluation, social return on investment (SROI) methodology offers a way of placing values on personal, social and community outcomes, not just economic outcomes. Developed in 2000, there have been calls for greater academic involvement in development of SROI, which to date has been more typically implemented in-house or by consultants. This protocol describes a systematic review of SROI analysis conducted on health and social care programmes which represent a significant sector of social enterprise internationally. The aims of the systematic review are to (1) identify the extent to which academics have adopted SROI methodology, (2) how academics have interpreted, used and developed SROI methodology and (3) to assess the quality of studies published under peer review.
The systematic review will include peer-reviewed studies since 2000 published in English. Search terms will be ‘social return on investment’ or ‘SROI’. Health and social care interventions will be identified in the initial screening given the proliferation of possible key words in these areas. Databases to be searched include Web of Science, Scopus, Medline, Social Care Online and National Institute for Health and Care Excellence. Two reviewers will independently conduct initial screening based on titles and abstracts against the inclusion criteria. Data extracted will include date of intervention, country, study design, aim of intervention/programme, participants and setting, health and social care measures used, and SROI ratio. The quality of studies will be assessed by two reviewers using a SROI quality framework designed for the purpose of this study.
The systematic review will review existing published academic literature; as such, ethics approval is not required for this study. A paper of the systematic review will be submitted to a peer-reviewed journal.
Diabetes mellitus (DM) is a major disease burden worldwide because it is associated with disabling and lethal complications. DM complication risk assessment and stratification is key to cost-effective management and tertiary prevention for patients with diabetes in primary care. Existing risk prediction functions were found to be inaccurate in Chinese patients with diabetes in primary care. This study aims to develop 10-year risk prediction models for total cardiovascular diseases (CVD) and all-cause mortality among Chinese patients with DM in primary care.
A 10-year cohort study on a population-based primary care cohort of Chinese patients with diabetes, who were receiving care in the Hospital Authority General Outpatient Clinic on or before 1 January 2008, were identified from the clinical management system database of the Hospital Authority. All patients with complete baseline risk factors will be included and followed from 1 January 2008 to 31 December 2017 for the development and validation of prediction models. The analyses will be carried out separately for men and women. Two-thirds of subjects will be randomly selected as the training sample for model development. Cox regressions will be used to develop 10-year risk prediction models of total CVD and all-cause mortality. The validity of models will be tested on the remaining one-third of subjects by Harrell’s C-statistics and calibration plot. Risk prediction models for diabetic complications specific to Chinese patients in primary care will enable accurate risk stratification, prioritisation of resources and more cost-effective interventions for patients with DM in primary care.
The study was approved by the Institutional Review Board of the University of Hong Kong—the Hospital Authority Hong Kong West Cluster (reference number: UW 15–258).