Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis

Objective: To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics. Design: A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed. Setting: Any developed country healthcare setting. Participants: Patients, healthcare professionals, managers, payers and academics. Intervention: Experiences and views of oral and intravenous bisphosphonates. Results: Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability. Conclusion: By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment

A questionnaire to identify patellofemoral pain in the community: an exploration of measurement properties

Background Community-based studies of patellofemoral pain (PFP) need a questionnaire tool that discriminates between those with and those without the condition. To overcome these issues, we have designed a self-report questionnaire which aims to identify people with PFP in the community. Methods Study designs: comparative study and cross-sectional study. Study population: comparative study: PFP patients, soft-tissue injury patients and adults without knee problems. Cross-sectional study: adults attending a science festival. Intervention: comparative study participants completed the questionnaire at baseline and two weeks later. Cross-sectional study participants completed the questionnaire once. The optimal scoring system and threshold was explored using receiver operating characteristic curves, test-retest reliability using Cohen’s kappa and measurement error using Bland-Altman plots and standard error of measurement. Known-group validity was explored by comparing PFP prevalence between genders and age groups. Results Eighty-four participants were recruited to the comparative study. The receiver operating characteristic curves suggested limiting the questionnaire to the clinical features and knee pain map sections (AUC 0.97 95 % CI 0.94 to 1.00). This combination had high sensitivity and specificity (over 90 %). Measurement error was less than the mean difference between the groups. Test–retest reliability estimates suggest good agreement (N = 51, k = 0.74, 95 % CI 0.52–0.91). The cross-sectional study (N = 110) showed expected differences between genders and age groups but these were not statistically significant. Conclusion A shortened version of the questionnaire, based on clinical features and a knee pain map, has good measurement properties. Further work is needed to validate the questionnaire in community samples

Cassini multi-instrument assessment of Saturn's polar cap boundary

We present the first systematic investigation of the polar cap boundary in Saturn's high-latitude magnetosphere through a multi-instrument assessment of various Cassini in situ data sets gathered between 2006 and 2009. We identify 48 polar cap crossings where the polar cap boundary can be clearly observed in the step in upper cutoff of auroral hiss emissions from the plasma wave data, a sudden increase in electron density, an anisotropy of energetic electrons along the magnetic field, and an increase in incidence of higher-energy electrons from the low-energy electron spectrometer measurements as we move equatorward from the pole. We determine the average level of coincidence of the polar cap boundary identified in the various in situ data sets to be 0.34° ± 0.05° colatitude. The average location of the boundary in the southern (northern) hemisphere is found to be at 15.6° (13.3°) colatitude. In both hemispheres we identify a consistent equatorward offset between the poleward edge of the auroral upward directed field-aligned current region of ~1.5–1.8° colatitude to the corresponding polar cap boundary. We identify atypical observations in the boundary region, including observations of approximately hourly periodicities in the auroral hiss emissions close to the pole. We suggest that the position of the southern polar cap boundary is somewhat ordered by the southern planetary period oscillation phase but that it cannot account for the boundary's full latitudinal variability. We find no clear evidence of any ordering of the northern polar cap boundary location with the northern planetary period magnetic field oscillation phase

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer

Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC): Supporting the transition from strategy to action.

In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and drug resistance, burden of disease, information on antibiotic use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC will strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC's first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with the need for creativity in the use of existing data and proxy measures, and linking to existing in-country networking infrastructure. SEDRIC will also promote the translation of technological innovations into public health solutions

Mx Scripts Library: Structural Equation Modeling Scripts for Twin and Family Data

Structural equation modeling (SEM) provides a flexible tool to carry out genetic analyses of family and twin data. The basic model which decomposes the variance between and within families for a particular trait into genetic and non-genetic components can be generalized to multivariate and/ or longitudinal data, incorporate sex differences in parameter estimates, and model the effects of measured environment, candidate genes or DNA marker data. We introduce a web-based library ( http://www.psy.vu.nl/mxbib ) of scripts for uni- and multivariate genetic epidemiological analyses, as well as for linkage and genetic association tests. The scripts are written to be used with the freely available software package Mx and provide a flexible and uniform approach to the analysis of data from relatives. © 2005 Springer Science+Business Media, Inc

Healthcare practitioners' views and experiences of barriers and facilitators to weight management interventions for adults with intellectual disabilities

Background Obesity is common in adults with intellectual disabilities, yet little is known about how weight management interventions are provided for this population. Methods Semi‐structured interviews were held with 14 healthcare practitioners involved in weight management interventions in an English county. A study topic guide was developed to elicit practitioners' views and experiences of barriers and facilitators to weight management for adults with intellectual disabilities. Responses were analysed using thematic analysis. Results Several barriers are involved in weight management for people with intellectual disabilities including communication challenges, general practitioners' lack of knowledge and awareness of weight management services, inconsistencies in caring support, resource constraints, wider external circumstances surrounding the individuals and motivational issues. Facilitators include reasonable adjustments to existing weight management services. However, there is a need for specialist weight management provision for people with intellectual disabilities. Conclusions This study provides suggestions for future research, policy and practice consideration

The North Staffordshire Osteoarthritis Project – NorStOP: Prospective, 3-year study of the epidemiology and management of clinical osteoarthritis in a general population of older adults

BACKGROUND: The clinical syndrome of joint pain and stiffness in older people is the commonest cause of disability and health care consultation in this age group. Yet there have been few prospective studies of its course over time and its impact on personal and social life. We plan a cohort study in the general population aged 50 years and over to determine the course and prognosis of hand, hip, knee and foot pain, and the impact of these syndromes on participation levels and health care use. METHODS: All patients aged 50 years and over registered with 3 local general practices are to be recruited to a population-based cohort study through the use of a two-stage mailing process. Participants will initially complete a "Health Survey" questionnaire. This will collect information on several areas of life including socio-demographics, general health, physical function, participation, and bodily pain. Those who state that they have experienced any hand problem or any pain in their hands, hips, knees, or feet in the previous 12 months, and also give permission to be re-contacted, will be mailed a "Regional Pains Survey" questionnaire which collects detailed information on the four selected body regions (hand, hips, knees, feet). Follow-up data for the three-year period subsequent to cohort recruitment will be collected through two sources: i) general practice medical records and ii) repeat mailed survey

Maternal obesity support services: a qualitative study of the perspectives of women and midwives

Background - Twenty percent of pregnant women in the UK are obese (BMI ≥ 30 kg/m2), reflecting the growing public health challenge of obesity in the 21st century. Obesity increases the risk of adverse outcomes during pregnancy and birth and has significant cost implications for maternity services. Gestational weight management strategies are a high priority; however the evidence for effective, feasible and acceptable weight control interventions is limited and inconclusive. This qualitative study explored the experiences and perceptions of pregnant women and midwives regarding existing support for weight management in pregnancy and their ideas for service development. Methods - A purposive sample of 6 women and 7 midwives from Doncaster, UK, participated in two separate focus groups. Transcripts were analysed thematically. Results - Two overarching themes were identified, 'Explanations for obesity and weight management' and 'Best care for pregnant women'. 'Explanations' included a lack of knowledge about weight, diet and exercise during pregnancy; self-talk messages which excused overeating; difficulties maintaining motivation for a healthy lifestyle; the importance of social support; stigmatisation; and sensitivity surrounding communication about obesity between midwives and their clients. 'Best care' suggested that weight management required care which was consistent and continuous, supportive and non-judgemental, and which created opportunities for interaction and mutual support between obese pregnant women. Conclusions - Women need unambiguous advice regarding healthy lifestyles, diet and exercise in pregnancy to address a lack of knowledge and a tendency towards unhelpful self-talk messages. Midwives expressed difficulties in communicating with their clients about their weight, given awareness that obesity is a sensitive and potentially stigmatising issue. This indicates more could be done to educate and support them in their work with obese pregnant women. Motivation and social support were strong explanatory themes for obesity and weight management, suggesting that interventions should focus on motivational strategies and social support facilitation