Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments

Fumaric acid esters (FAE) are licensed for the treatment of moderate to severe psoriasis in Germany but are also used off-label in many other countries. We conducted this systematic review to synthesize the highest quality evidence for the benefits and risks of FAE for psoriasis. Our primary outcomes were change in PASI score and drop-out rates due to adverse effects. Randomised controlled trials (RCTs) of FAE or dimethyl fumarate were included, with no restriction on age or psoriasis subtype. We searched The Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library, MEDLINE, EMBASE, LILACS, five trials registers and handsearched six conference proceedings. Six RCTs with 544 participants were included, four of which were published only as abstracts or brief reports, limiting study reporting. Five RCTs compared FAE with placebo and all demonstrated benefit in favour of FAE but meta-analysis was only possible for PASI 50 after 12-16 weeks, which was achieved by 64% of participants on FAE compared to 14% on placebo (risk ratio (RR) 4.55; 95% CI 2.80 to 7.40; 2 studies; 247 participants; low quality evidence). There was no difference in drop-out rates due to adverse effects (RR 5.36, 95% CI 0.28 to 102.12; 1 study; 27 participants; very low-quality evidence and wide confidence interval). More participants experienced nuisance adverse effects with FAE (76%) compared to placebo (16%) (RR 4.72, 95% CI 2.45 to 9.08; 1 study; 99 participants; moderate-quality evidence), mainly abdominal pain, diarrhoea and flushing. One head-to-head study of very low quality evidence comparing FAE with methotrexate reported comparable efficacy and drop-out rates, although FAE caused more flushing. The evidence in this review was limited and must be interpreted with caution; better designed and reported studies are needed

Feasibility and acceptability of text messaging to support antenatal healthcare in Iraqi pregnant women: a pilot study

Objective: To determine the feasibility and acceptability of mobile health technology and its potential to improve antenatal care (ANC) services in Iraq. Methods: This was a controlled experimental study conducted at primary health care centers. One hundred pregnant women who attended those centres for ANC were exposed to weekly text messages varying in content, depending on the week of gestation, while 150 women were recruited for the unexposed group. The number of ANC visits in the intervention and control groups, was the main outcome measure. The Mann-Whitney test and the Poisson regression model were the two main statistical tests used. Results: More than 85% of recipients were in agreement with the following statements: “the client recommends this program for other pregnant women”, “personal rating for the message as a whole” and “obtained benefit from the messages”. There was a statistically significant increase in the median number of antenatal clinic visits from two to four per pregnancy, in addition to being relatively of low cost, and could be provided for a larger population with not much difference in the efforts. Conclusions: Text messaging is feasible, low cost and reasonably acceptable to Iraqi pregnant women, and encourages their ANC visits

SARS-like WIV1-CoV poised for human emergence

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV highlights the continued risk of cross-species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS-like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1-CoV. Both full-length and chimeric WIV1-CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS-based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1-related viruses and the need for continued study and surveillance

Protocol for 'Seal or Varnish' (SoV) trial: A randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay

Background Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. Methods/design The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6–7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. Discussion The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the$/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia:$1425, India: $1489, Vietnam:$1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from$237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to$749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to$241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING: The Bill and Melinda Gates Foundation and World Health Organization

Preventing disease through opportunistic, rapid engagement by primary care teams using behaviour change counselling (PRE-EMPT): protocol for a general practice-based cluster randomised trial

BACKGROUND: Smoking, excessive alcohol consumption, lack of exercise and an unhealthy diet are the key modifiable factors contributing to premature morbidity and mortality in the developed world. Brief interventions in health care consultations can be effective in changing single health behaviours. General Practice holds considerable potential for primary prevention through modifying patients' multiple risk behaviours, but feasible, acceptable and effective interventions are poorly developed, and uptake by practitioners is low. Through a process of theoretical development, modeling and exploratory trials, we have developed an intervention called Behaviour Change Counselling (BCC) derived from Motivational Interviewing (MI). This paper describes the protocol for an evaluation of a training intervention (the Talking Lifestyles Programme) which will enable practitioners to routinely use BCC during consultations for the above four risk behaviours. METHODS/DESIGN: This cluster randomised controlled efficacy trial (RCT) will evaluate the outcomes and costs of this training intervention for General Practitioners (GPs) and nurses. Training methods will include: a practice-based seminar, online self-directed learning, and reflecting on video recorded and simulated consultations. The intervention will be evaluated in 29 practices in Wales, UK; two clinicians will take part (one GP and one nurse) from each practice. In intervention practices both clinicians will receive training. The aim is to recruit 2000 patients into the study with an expected 30% drop out. The primary outcome will be the proportion of patients making changes in one or more of the four behaviours at three months. Results will be compared for patients seeing clinicians trained in BCC with patients seeing non-BCC trained clinicians. Economic and process evaluations will also be conducted. DISCUSSION: Opportunistic engagement by health professionals potentially represents a cost effective medical intervention. This study integrates an existing, innovative intervention method with an innovative training model to enable clinicians to routinely use BCC, providing them with new tools to encourage and support people to make healthier choices. This trial will evaluate effectiveness in primary care and determine costs of the intervention

Measuring clinical skills in agenda-mapping (EAGL-I)

Objective To develop and validate the Evaluation of AGenda-mapping skilL Instrument (EAGL-I). Methods EAGL-I was constructed after a literature review and piloting. Simulated consultation recordings were collected in a workshop with third-year medical students at three time points: once pre-teaching, twice post-teaching. Three raters used EAGL-I to assess student agenda-mapping. We examined reliability, ability to detect change and predict full expression of patients’ agendas. Results EAGL-I scores represented reliable assessment of agenda-mapping (Ep2 = 0.832; φ = 0.675). Generalizability coefficients across items (Ep2 = 0.836) and raters (φ = 0.797 two raters) were acceptable. A one-way repeated measure ANOVA with post hoc analysis found a statistically significant difference between the pre-teaching occasion of measurement and each post-teaching occasion (p < 0.001) and no significant difference between the two post-teaching occasions (p = 0.085). Multilevel logistic regression show scores predict expression of scripted hidden agendas irrespective of occasions, or patient scenario (n = 60, p = 0.005). Conclusion Evidence of measure validation is shown. Reliability is optimised when two or more raters use EAGL-I and agenda-mapping has been taught. EAGL-I appears sensitive to change. Higher scores predict the likelihood that a patient will disclose their full agenda in a simulated environment. Practice implications A validated tool for measuring agenda-mapping in teaching and research is now available

Personalised risk communication for informed decision making about taking screening tests

Background. There is a trend towards greater patient involvement in healthcare decisions. Although screening is usually perceived as good for the health of the population, there are risks associated with the tests involved. Achieving both adequate involvement of consumers and informed decision making are now seen as important goals for screening programmes. Personalised risk estimates have been shown to be effective methods of risk communication. Objectives. To assess the effects of personalised risk communication on informed decision making by individuals taking screening tests. We also assess individual components that constitute informed decisions. Search methods. Two authors searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2012), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHOST) and PsycINFO (OvidSP) without language restrictions. We searched from 2006 to March 2012. The date ranges for the previous searches were from 1989 to December 2005 for PsycINFO and from 1985 to December 2005 for other databases. For the original version of this review, we also searched CancerLit and Science Citation Index (March 2001). We also reviewed the reference lists and conducted citation searches of included studies and other systematic reviews in the field, to identify any studies missed during the initial search. Selection criteria. Randomised controlled trials incorporating an intervention with a 'personalised risk communication element’ for individuals undergoing screening procedures, and reporting measures of informed decisions and also cognitive, affective, or behavioural outcomes addressing the decision by such individuals, of whether or not to undergo screening. Data collection and analysis. Two authors independently assessed each included trial for risk of bias, and extracted data. We extracted data about the nature and setting of interventions, and relevant outcome data. We used standard statistical methods to combine data using RevMan version 5, including analysis according to different levels of detail of personalised risk communication, different conditions for screening, and studies based only on high-risk participants rather than people at 'average’ risk. Main results. We included 41 studies involving 28,700 people. Nineteen new studies were identified in this update, adding to the 22 studies included in the previous two iterations of the review. Three studies measured informed decision with regard to the uptake of screening following personalised risk communication as a part of their intervention. All of these three studies were at low risk of bias and there was strong evidence that the interventions enhanced informed decision making, although with heterogeneous results. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices, compared to 20.2% (229/1135) of participants who received generic risk information. The overall odds ratios (ORs) for informed decision were 4.48 (95% confidence interval (CI) 3.62 to 5.53 for fixed effect) and 3.65 (95% CI 2.13 to 6.23 for random effects). Nine studies measured increase in knowledge, using different scales. All of these studies showed an increase in knowledge with personalised risk communication. In three studies the interventions showed a trend towards more accurate risk perception, but the evidence was of poor quality. Four out of six studies reported non-significant changes in anxiety following personalised risk communication to the participants. Overall there was a small non-significant decrease in the anxiety scores. Most studies (32/41) measured the uptake of screening tests following interventions. Our results (OR 1.15 (95% CI 1.02 to 1.29)) constitute low quality evidence, consistent with a small effect, that personalised risk communication in which a risk score was provided (6 studies) or the participants were given their categorised risk (6 studies), increases uptake of screening tests. Authors' conclusions. There is strong evidence from three trials that personalised risk estimates incorporated within communication interventions for screening programmes enhance informed choices. However the evidence for increasing the uptake of such screening tests with similar interventions is weak, and it is not clear if this increase is associated with informed choices. Studies included a diverse range of screening programmes. Therefore, data from this review do not allow us to draw conclusions about the best interventions to deliver personalised risk communication for enhancing informed decisions. The results are dominated by findings from the topic area of mammography and colorectal cancer. Caution is therefore required in generalising from these results, and particularly for clinical topics other than mammography and colorectal cancer screening

Recruitment to diagnosis of urinary tract infections in young children (DUTY) study: an evaluation of the successful methods used in a primary care, prospective cohort study. [Abstract]

DUTY is a prospective cohort study to derive a clinical algorithm for diagnosis of urinary tract infections in acutely unwell children in primary care. It provides an example of successful recruitment to a complex paediatric study, requiring the collection of a urine sample from young, unwell children. The aim is to describe and evaluate factors that contributed to its success from a study management and recruiter perspective