Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study.

BACKGROUND: Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. METHODS: Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson's correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. RESULTS: EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = - 0.18), PR (r = - 0.25), and AR (r = - 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). CONCLUSION: These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.

A comparative assessment of two tools designed to support patient safety culture in UK general practice.

BACKGROUND: The NHS has recognised the importance of a high quality patient safety culture in the delivery of primary health care in the rapidly evolving environment of general practice. Two tools, PC-SafeQuest and MapSaf, were developed with the intention of assessing and improving patient safety culture in this setting. Both have been made widely available through their inclusion in the Royal College of General Practitioners' Patient Safety Toolkit and our work offerss a timely exploration of the tools to inform practice staff as to how each might be usefully applied and in which circumstances. Here we present a comparative analysis of their content, and describe the perspectives of staff on their design, outputs and the feasibility of their sustained use. METHODS: We have used a content analysis to provide the context for the qualitative study of staff experiences of using the tools at a representative range of practices recruited from across the Midlands (UK). Data was collected through moderated focus groups using an identical topic guide. RESULTS: A total of nine practices used the PC-SafeQuest tool and four the MapSaf tool. A total of 159 staff completed the PC-SafeQuest tool 52 of whom took part in the subsequent focus group discussions, and 25 staff completed the MapSaf tool all of whom contributed to the focus group discussions. PC-SafeQuest was perceived as quick and easy to use with direct questions pertinent to the work of GP practices providing useful quantitative insight into important areas of safety culture. Though MaPSaF was more logistically challenging, it created a forum for synchronous cross- practice discussions raising awareness of perceptions of safety culture across the practice team. CONCLUSIONS: Both tools were able to promote reflective and reflexive practice either in individual staff members or across the broader practice team and the oversight they granted provided useful direction for senior staff looking to improve patient safety. Because PC SafeQuest can be easily disseminated and independently completed it is logistically suited to larger practice organisations, whereas the MapSaf tool lends itself to smaller practices where assembling staff in a single workshop is more readily achieved.

Barriers and facilitators to preventive interventions for the development of obstetric fistulas among women in sub-Saharan Africa: a systematic review.

BACKGROUND: Obstetric fistula is a debilitating childbearing injury that results from poorly managed obstructed labour, leading to the development of holes between the vagina and bladder and/or rectum. Effects of this injury are long-lasting, as women become incontinent and are often marginalised from their communities. Despite continuous occurrence of this injury in lower-income countries, it is preventable, as evidenced in high-income countries. This systematic review aims to identify and understand barriers and facilitators to interventions aimed at the prevention of obstetric fistulas in sub-Saharan African women. METHODS: Electronic databases and grey literature were searched. We included studies written in English that discussed interventions to prevent obstetric fistulas implemented in sub-Saharan Africa, and their associated barriers and facilitators. Quality of the studies was assessed, and data including: country of implementation, preventive interventions, and barriers and facilitators to the interventions were extracted. They were then categorised based on the Three Phase Delay Model. RESULTS: Our search yielded 537 studies, of which 18 were included from sub-Saharan countries including Ethiopia, Nigeria, and Zambia. The most noted barrier to prevention addressed the first phase of delay: the decision to seek care, particularly lack of awareness of the dangers of unsupervised labours. The most noted facilitator addressed the decision to seek care and the quality of care received at a facility, through partnerships between health facilities and governments, and other organisations that provided both financial and resource support. CONCLUSION: Despite being categorised by the three phases of the delay model, barriers and facilitators were found to play a role in multiple phases. The topic of obstetric fistula needs to be researched more extensively, particularly the effectiveness of preventive interventions.

Effectiveness of health education as an intervention designed to prevent female genital mutilation/cutting (FGM/C): a systematic review.

BACKGROUND: Female Genital Mutilation/Cutting (FGM/C) is a harmful practice that violates the human rights of women and girls. Despite global efforts to restrict the practice, there have been few reports on major positive changes to the problem. Health education interventions have been successful in preventing various health conditions and promoting service use. They have also been regarded as promising interventions for preventing FGM/C. The objective of this systematic review is to synthesise findings of studies about effectiveness of health education as an intervention to prevent FGM/C. METHODS: The electronic databases searched were MEDLINE, EMBASE, Cochrane library, Web of Science, Psych INFO, CINAHL and ASSIA. Our search included papers published in the English language without date limits. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). A predesigned data recording form was used to extract data from the included studies which were summarised by comparing similar themes. RESULTS: Twelve out of 359 individual studies met our inclusion criteria. Seven studies were quantitative, three were qualitative and two used mixed methods. Six studies tested before and after the interventions, four studies assessed the effectiveness of previous interventions used by different research teams and two studies endorsed the intervention. Four main factors emerged and were associated with facilitating or hindering the effectiveness of health education interventions: sociodemographic factors; socioeconomic factors; traditions and beliefs; and intervention strategy, structure and delivery. CONCLUSIONS: It is vital to target factors associated with facilitating or hindering the effectiveness of health education for FGM/C. This increases the possibility of effective, collective change in behaviour and attitude which leads to the sustainable prevention of FGM/C and ultimately the improved reproductive health and well-being of individuals and communities.

Heart failure and chronic obstructive pulmonary disease multimorbidity at hospital discharge transition: a study of patient and carer experience.

BACKGROUND: Care for patients with multimorbidity represents a major challenge not only for patients and carers but to health-care systems. Hospital discharge transition is a critical point at which challenges for multimorbidity may amplify. OBJECTIVES: The main objective of the study was to explore the experiences of heart failure (HF) and chronic obstructive pulmonary disease (COPD) multimorbid patients and their carers on hospital discharge. Secondary objectives included identification of gaps in the health care of multimorbidity and optimal solutions from patients and carers' perspectives. DESIGN: Mixed methods were applied to collect data using patient self-completion questionnaire from an adapted version of the American Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey and in-depth interviews. SETTING: Participants were recruited from two cardiology and respiratory wards at a large regional hospital in England, and all had a multimorbidity diagnosis of COPD and HF. RESULTS AND CONCLUSIONS: Findings revealed that patients experienced difficulties in their communication with health-care professionals and there were specific challenges with information about medication. Qualitative descriptions revealed that experiences fell into two main categories: (i) information transfer to patients with multimorbidity in terms of issues with medication and clarity of information on diagnosis and (ii) communication and continuity of care after discharge. Respondents highlighted gaps in the management of patients with multimorbidity of HF and COPD at the critical time of care transition. They suggested the need for a comprehensive, coordinated and integrated approach to incorporate patients, carers and staff preferences for treatment on discharge from hospital.

Multi-drug therapy in chronic condition multimorbidity: a systematic review.

BACKGROUND: Older populations often suffer from multimorbidity and guidelines for each condition are often associated with recommended drug therapy management. Yet, how different and specific multimorbidity is associated with number and type of multi-drug therapies in general populations is unknown. AIM: The aim of this systematic review was to synthesize the current evidence on patterns of multi-drug prescribing in family practice. METHODS: A systematic review on six common chronic conditions: diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), osteoarthritis and depression was conducted, with a focus on studies which looked at any potential combination of two or more multimorbidity. Studies were identified from searches of MEDLINE, EMBASE, PsychINFO, the Allied and Complementary Medicine Database (AMED) and the Health Management Information Consortium (HMIC) databases from 1960 to 2013. RESULTS: A total of eleven articles were selected based on study criteria. Our review identified very few specific studies which had explicitly investigated the association between multimorbidity and multi-drug therapy. Relevant chronic conditions literature showed nine observational studies and two reviews of comorbid depression drug treatment. Most (seven) of the articles had focused on the chronic condition and comorbid depression and whether antidepressant management had been optimal or not, while four studies focused on other multimorbidities mainly heart failure, COPD and diabetes. CONCLUSIONS: Very few studies have investigated associations between specific multimorbidity and multi-drug therapy, and most currently focus on chronic disease comorbid depression outcomes. Further research needs to identify this area as key priority for older populations who are prescribed high levels of multiple drug therapy.

Mosaic segmentation, COPD and CHF multimorbidity and hospital admission costs: a clinical linkage study.

BACKGROUND: How multimorbidity and socio-economic factors influence healthcare costs is unknown. Geo-demographic profiling system, Mosaic, which adds to socio-economic factors, provides the potential for an investigation of the relationship with multimorbidity, and their influence on healthcare costs. METHODS: Using chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) registers from 53 general practices for a population aged 40 years and over in Stoke-on-Trent, England (N = 10,113), were linked to hospital admissions data and Healthcare Resource Groups as a measure of hospital cost (2007-09). Eleven Mosaic groups were linked on the basis of individual patients' post codes. RESULTS: The COPD and CHF multimorbid group (n = 763) had the highest proportion with at least one hospital admission in the 3-year time period (n = 550, 72%), compared with the index COPD (56%) and CHF (66%) groups. Multimorbid patients had significantly higher mean costs for hospital admission (£4896) compared with the index COPD (£2769) or CHF (£3876). The associations between multimorbid groups and hospital admission costs compared with index groups varied by different Mosaic groups. CONCLUSIONS: CHF and COPD multimorbidity is associated with high costs, and average hospital admission costs vary by Mosaic segmentation. Multimorbidity and Mosaic provide an innovative basis for developing and targeting healthcare interventions in high-hospital-cost patients.

Six aspects of female genital mutilation education (SAFE) model: findings from a qualitative study.

OBJECTIVES: Recent figures show that over 200 million women and girls, globally, live with the consequences of female genital mutilation (FGM). Complex debilitating physical, psychological and social problems result from the practice. Health education interventions have proven to be essential in both preventing the practice and informing support of survivors. In this study, we aimed to explore factors that affect the effectiveness of health education interventions. DESIGN: A generic qualitative approach was applied using semistructured individual and focus group interviews with women and men from communities with a history of FGM in Birmingham, UK. Framework analysis was used to group recurring themes from the data. Intersectionality was used as a theoretical lens to synthesise findings. PARTICIPANTS: Twenty-one individuals (18 women and 3 men) participated in semistructured individual and focus group interviews about their views and experiences of health and well-being intervention programmes related to FGM. RESULTS: Six themes emerged from the data and were developed into a model of issues relating to FGM education. These six themes are (1) active communication, (2) attitudes and beliefs, (3) knowledge about FGM, (4) social structures, (5) programme approach and (6) the better future. A combined discussion of all these issues was compressed into three groupings: social structures, culture and media. CONCLUSION: The results of this study depict aspects associated with FGM education that should be considered by future interventions aiming to prevent the practice and inform support services for survivors in a holistic way.

Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely regarded as one risk factor, which influences chronic kidney disease (CKD) progression. However, previous literature reviews have not quantified the risk in moderate to severe CKD patients. OBJECTIVE: To estimate the strength of association between chronic NSAID use and CKD progression. METHODS: We conducted a systematic review and meta-analysis of observational general practice or population studies featuring patients aged 45 years and over. The electronic databases searched were MEDLINE, EMBASE, Cochrane, AMED, BNI and CINAHL until September 2011 without date or language restrictions. Searches included the reference lists of relevant identified studies, WEB of KNOWLEDGE, openSIGLE, specific journals, the British Library and expert networks. For relevant studies, random effects meta-analysis was used to estimate the association between NSAID use and accelerated CKD progression (estimated glomerular filtration rate decline ≥ 15 ml/min/1.73 m2). RESULTS: From a possible 768 articles, after screening and selection, seven studies were identified (5 cohort, 1 case-control and 1 cross-sectional) and three were included in the meta-analysis. Regular-dose NSAID use did not significantly affect the risk of accelerated CKD progression; pooled odds ratio (OR) = 0.96 (95%CI: 0.86-1.07), but high-dose NSAID use significantly increased the risk of accelerated CKD progression; pooled OR = 1.26 (95%CI: 1.06-1.50). CONCLUSIONS: The avoidance of NSAIDs in the medium term is unnecessary in patients with moderate to severe CKD, if not otherwise contraindicated. As the definition of high-dose of NSAID use remains unclear, the lowest effective dose of NSAIDs should be prescribed where indicated.

Breast Cancer Index Is a Predictive Biomarker of Treatment Benefit and Outcome from Extended Tamoxifen Therapy: Final Analysis of the Trans-aTTom Study.

PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor-positive (HR+) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance. EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69-1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N+ subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14-0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (-1.2% absolute benefit; HR, 1.11; 95% CI, 0.76-1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N+/HER2- subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15-0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849). CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR+ N+ patients with HER2- disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes.

"It's the First Barrier" - Lack of Common Language a Major Obstacle When Accessing/Providing Healthcare Services Across Europe.

International migration is shaping and changing urban areas as well as impacting on healthcare access and provision in Europe. To investigate how residents of superdiverse neighborhoods put together their healthcare, we conducted qualitative interviews with 76 healthcare providers and 160 residents in four European cities - Bremen, Germany; Birmingham, UK; Lisbon, Portugal and Uppsala, Sweden, between September 2015 and April 2017. A common theme arising from the data was language and communication obstacles, with both healthcare providers and users experiencing language difficulties, despite all four countries having interpretation policies or guidelines to address language barriers in healthcare. Official interpreter services were seen to be unreliable and sometimes of poor quality, leading to a reliance on informal interpretation. Some coping strategies used by both service providers and users led to successful communication despite the lack of a common language. Where communication failed, this led to feelings of dissatisfaction and frustration among both users and providers. Language difficulties came up across all participating countries even though this was not prompted by interview questions, which highlights the widespread nature of language barriers and communication barriers and the need to address them in order to promote equal accessibility to good quality healthcare.

A Patient Safety Toolkit for Family Practices.

OBJECTIVE: Major gaps remain in our understanding of primary care patient safety. We describe a toolkit for measuring patient safety in family practices. METHODS: Six tools were used in 46 practices. These tools were as follows: National Health Service Education for Scotland Trigger Tool, National Health Service Education for Scotland Medicines Reconciliation Tool, Primary Care Safequest, Prescribing Safety Indicators, Patient Reported Experiences and Outcomes of Safety in Primary Care, and Concise Safe Systems Checklist. RESULTS: Primary Care Safequest showed that most practices had a well-developed safety climate. However, the trigger tool revealed that a quarter of events identified were associated with moderate or substantial harm, with a third originating in primary care and avoidable. Although medicines reconciliation was undertaken within 2 days in more than 70% of cases, necessary discussions with a patient/carer did not always occur. The prescribing safety indicators identified 1435 instances of potentially hazardous prescribing or lack of recommended monitoring (from 92,649 patients). The Concise Safe Systems Checklist found that 25% of staff thought that their practice provided inadequate follow-up for vulnerable patients discharged from hospital and inadequate monitoring of noncollection of prescriptions. Most patients had a positive perception of the safety of their practice although 45% identified at least one safety problem in the past year. CONCLUSIONS: Patient safety is complex and multidimensional. The Patient Safety Toolkit is easy to use and hosted on a single platform with a collection of tools generating practical and actionable information. It enables family practices to identify safety deficits that they can review and change procedures to improve their patient safety across a key sets of patient safety issues.

Trends in the costs of drugs launched in the UK between 1981 and 2015: an analysis of the launch price of drugs in five disease areas.

OBJECTIVES: To investigate the trend in the launch price of new drugs for five common health conditions. DESIGN: Cross-sectional study using data on new drugs launched in the UK between 1981 and 2015 for hypertension, asthma, rheumatoid arthritis, schizophrenia and colorectal cancer. DATA AND SOURCES: All drugs marketed in the UK between 1981 and 2015 (inclusive), and licensed specifically for the treatment of one of the five chosen conditions were included in the study. Newly launched medicines and their launch prices were identified by hand-searching all editions of the British National Formulary in addition to searching the websites of relevant regulatory agencies (European Medicines Agency and Medicines and Healthcare products Regulatory Agency). The launch price in UK pounds for a 28-day supply of each medicine at a typical or usual maintenance dose was adjusted for the effects of general inflation using the gross domestic product deflator series. RESULTS: 104 drugs were included in our study with a mean inflation-adjusted 28-day launch price of £288 (SD £678). The launch price of new drugs varied significantly across the five conditions, with drugs for hypertension having the lowest mean price (£27) and drugs for colorectal cancer having the highest mean price (£1590) (p<0.001). There were large increases in launch prices across the study period, but the magnitude and pattern was markedly different between therapeutic areas. Biological drugs represented 13.5% of all included drugs and had a significantly higher launch price than non- biological drugs (£1233 vs £141, p<0.001). 22.1% of included drugs were first-of-kind and had a significantly higher launch price than follow-on drugs (£768 vs £151) (p<0.0001). CONCLUSION: Drugs prices continue to increase across different therapeutic areas. This has some association with novelty, but, it is not clear if this increase in price is associated with medical benefits.

Past speculations of future health technologies: a description of technologies predicted in 15 forecasting studies published between 1986 and 2010.

OBJECTIVE: To describe and classify health technologies predicted in forecasting studies. DESIGN AND METHODS: A portrait describing health technologies predicted in 15 forecasting studies published between 1986 and 2010 that were identified in a previous systematic review. Health technologies are classified according to their type, purpose and clinical use; relating these to the original purpose and timing of the forecasting studies. DATA SOURCES: All health-related technologies predicted in 15 forecasting studies identified in a previously published systematic review. MAIN OUTCOME MEASURE: Outcomes related to (1) each forecasting study including country, year, intention and forecasting methods used and (2) the predicted technologies including technology type, purpose, targeted clinical area and forecast timeframe. RESULTS: Of the 896 identified health-related technologies, 685 (76.5%) were health technologies with an explicit or implied health application and included in our study. Of these, 19.1% were diagnostic or imaging tests, 14.3% devices or biomaterials, 12.6% information technology systems, eHealth or mHealth and 12% drugs. The majority of the technologies were intended to treat or manage disease (38.1%) or diagnose or monitor disease (26.1%). The most frequent targeted clinical areas were infectious diseases followed by cancer, circulatory and nervous system disorders. The most frequent technology types were for: infectious diseases-prophylactic vaccines (45.8%), cancer-drugs (40%), circulatory disease-devices and biomaterials (26.3%), and diseases of the nervous system-equally devices and biomaterials (25%) and regenerative medicine (25%). The mean timeframe for forecasting was 11.6 years (range 0-33 years, median=10, SD=6.6). The forecasting timeframe significantly differed by technology type (p=0.002), the intent of the forecasting group (p<0.001) and the methods used (p<001). CONCLUSION: While description and classification of predicted health-related technologies is crucial in preparing healthcare systems for adopting new innovations, further work is needed to test the accuracy of predictions made.

Evaluating the Functional Results and Complications of Autograft vs Allograft Use for Reconstruction of the Anterior Cruciate Ligament: A Systematic Review.

The aim of our review is to identify the reconstruction technique that has a superior functional outcome and decreased number of complications for the anterior cruciate ligament (ACL). We have divided our review into 2 sections. Our primary question evaluates the functional results and complications of autografts compared to allografts for ACL reconstruction. Our subsidiary question evaluates the functional results and complications of bone-patellar tendon-bone (BPTB) autografts compared to hamstring tendon autografts. We conducted a systematic review (SR) based on high quality evidence provided by Cochrane, PubMed and National Health Service evidence searches for papers comparing different ACL reconstruction techniques. Results from 2 primary studies, 1 SR and 1 meta-analysis showed no significant statistical difference when comparing clinical outcomes such as pain, range of motion, laxity, International Knee Documentation Committee score, single assessment numerical evaluation score, Tegner activity score and patient reported satisfaction with regards to autografts vs allografts. Allografts had worse outcomes for postoperative tibial tunnelling and graft failure. Results of 3 SRs showed statistically significant differences in incidence of anterior knee pain, kneeling pain and knee stability, which were all found to be greater amongst those who had received a BPTB autograft. Knee extension was significantly reduced in patients with BPTB grafts when compared to patients with Hamstring tendon autografts. However, with regards to return to prior levels of activity, there was no statistically significant difference between those that received BPTB autografts and those that received Hamstring tendon autografts. Autograft reconstruction of the ACL was shown to provide better postoperative outcomes when compared to allograft reconstruction, although the difference was not statistically significant. When researching different autograft options BPTB autografts were associated with greater pain but also greater stability of the knee joint postoperatively when compared to hamstring tendon autografts.

Patients' evaluations of patient safety in English general practices: a cross-sectional study.

BACKGROUND: Description of safety problems and harm in general practices has previously relied on information from health professionals, with scarce attention paid to experiences of patients. AIM: To examine patient-reported experiences and outcomes of patient safety in primary care. DESIGN AND SETTING: Cross-sectional study in 45 general practices across five regions in the north, centre, and south of England. METHOD: A version of the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire was sent to a random sample of 6736 patients. Main outcome measures included 'practice activation' (what a practice does to create a safe environment); 'patient activation' (how proactive are patients in ensuring safe healthcare delivery); 'experiences of safety events' (safety errors); 'outcomes of safety' (harm); and 'overall perception of safety' (how safe patients rate their practice). RESULTS: Questionnaires were returned by 1244 patients (18.4%). Scores were high for 'practice activation' (mean [standard error] = 80.4 out of 100 [2.0]) and low for 'patient activation' (26.3 out of 100 [2.6]). Of the patients, 45% reported experiencing at least one safety problem in the previous 12 months, mostly related to appointments (33%), diagnosis (17%), patient provider communication (15%), and coordination between providers (14%). Twenty-three per cent of the responders reported some degree of harm in the previous 12 months. The overall assessment of level of safety of practices was generally high (86.0 out of 100 [16.8]). CONCLUSION: Priority areas for patient safety improvement in general practices in England include appointments, diagnosis, communication, coordination, and patient activation.

Accuracy of pharmaceutical company licensing predictions: projected versus actual licensing dates.

OBJECTIVES: To determine the accuracy of pharmaceutical companies' predictions of drug licensing timeframes for their products in late stage clinical development. METHODS: We compared predicted licensing dates provided to the National Institute for Health Research Horizon Scanning Research and Intelligence Centre by pharmaceutical companies against actual marketing authorisation application (MAA) and marketing authorisation (MA) dates published by the European Medicines Agency for drugs granted authorisation between 2009 and 2013. KEY FINDINGS: One hundred and twenty-three drugs met our inclusion criteria. About 78% were new drugs and 16% had orphan designation. Less than half (44%) and less than a quarter (24%) of MAA and MA predictions respectively were considered accurate (same month or 1 month either side of the actual date). Pharmaceutical companies were significantly more accurate in predicting MAA dates than MA dates (P < 0.001). For accurate predictions, the mean duration between the prediction being made and the actual MAA and MA dates were 17.5 and 18.7 months respectively. Out of the total 108 MA predictions, almost two-thirds (65.4%, 16/26) of short-term predictions (made in the 2 years prior to the actual MA) were accurate. For predicted dates that were earlier than the actual MA date, there was a positive relationship between accuracy and the time between the prediction and authorisation. CONCLUSIONS: Even in predicting near events from well-informed sources, accuracy is imperfect. There appears to be an optimum time for the provision of accurate information on predicted MAA and MA dates for drugs. This information is crucial for effective early awareness and alert activities.

Past speculations of the future: a review of the methods used for forecasting emerging health technologies.

OBJECTIVES: Forecasting can support rational decision-making around the introduction and use of emerging health technologies and prevent investment in technologies that have limited long-term potential. However, forecasting methods need to be credible. We performed a systematic search to identify the methods used in forecasting studies to predict future health technologies within a 3-20-year timeframe. Identification and retrospective assessment of such methods potentially offer a route to more reliable prediction. DESIGN: Systematic search of the literature to identify studies reported on methods of forecasting in healthcare. PARTICIPANTS: People are not needed in this study. DATA SOURCES: The authors searched MEDLINE, EMBASE, PsychINFO and grey literature sources, and included articles published in English that reported their methods and a list of identified technologies. MAIN OUTCOME MEASURE: Studies reporting methods used to predict future health technologies within a 3-20-year timeframe with an identified list of individual healthcare technologies. Commercially sponsored reviews, long-term futurology studies (with over 20-year timeframes) and speculative editorials were excluded. RESULTS: 15 studies met our inclusion criteria. Our results showed that the majority of studies (13/15) consulted experts either alone or in combination with other methods such as literature searching. Only 2 studies used more complex forecasting tools such as scenario building. CONCLUSIONS: The methodological fundamentals of formal 3-20-year prediction are consistent but vary in details. Further research needs to be conducted to ascertain if the predictions made were accurate and whether accuracy varies by the methods used or by the types of technologies identified.

Outcome measures in intervention trials for adults with autism spectrum disorders; a systematic review of assessments of core autism features and associated emotional and behavioural problems.

A systematic review was conducted of outcome measures used in treatment trials for older adolescents and adults with autism spectrum disorders (ASDs). Of 818 titles only 30 articles (19 of which involved pharmacological treatments) were identified that met inclusion criteria (sample size > 5; mean age of group > 15 years; mean IQ > 30; ASD diagnosis confirmed; use of objective ASD outcome measures; focus on symptoms core to or typically associated with ASDs). Selected studies included randomized and placebo-controlled trials, retrospective assessment studies, case series and open label or case-control trials. Use of outcome measures varied with frequent use of non-standardized assessments, very little use of measures designed specifically for individuals with ASD or of instruments focusing on core ASD deficits, such as communication or social functioning. Most commonly used were the Clinical Global Impression (CGI) rating scale and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The strengths or deficiencies of the outcome measures used were not systematically evaluated. Although there are now many well controlled treatment trials for children with ASDs, adult intervention research is very limited. The lack of valid and reliable outcome measures for adults with ASDs compromises attempts at treatment evaluation.

Analgesia dose prescribing and estimated glomerular filtration rate decline: a general practice database linkage cohort study.

OBJECTIVE: We aimed to quantify the short-term effect of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and paracetamol analgesia dose prescribing on estimated glomerular filtration rate (eGFR) decline in the general practice population. DESIGN: A population-based longitudinal clinical data linkage cohort study. SETTING: Two large general practices in North Staffordshire, UK. PARTICIPANTS: Patients aged 40 years and over with ≥2 eGFR measurements spaced ≥90 days apart between 1 January 2009 and 31 December 2010 were selected. EXPOSURE: Using WHO Defined Daily Dose standardised cumulative analgesia prescribing, patients were categorised into non-user, normal and high-dose groups. OUTCOME MEASURE: The primary outcome was defined as a >5 mL/min/1.73 m(2)/year eGFR decrease between the first and last eGFR. Logistic regression analyses were used to estimate risk, adjusting for sociodemographics, comorbidity, baseline chronic kidney disease (CKD) status, renin-angiotensin-system inhibitors and other analgesia prescribing. RESULTS: There were 4145 patients (mean age 66 years, 55% female) with an analgesia prescribing prevalence of 17.2% for NSAIDs, 39% for aspirin and 22% for paracetamol and stage 3-5 CKD prevalence was 16.1% (n=667). Normal or high-dose NSAID and paracetamol prescribing was not significantly associated with eGFR decline. High-dose aspirin prescribing was associated with a reduced risk of eGFR decline in patients with a baseline (first) eGFR ≥60 mL/min/1.73 m(2); OR=0.52 (95% CI 0.35 to 0.77). CONCLUSIONS: NSAID, aspirin and paracetamol prescribing over 2 years did not significantly affect eGFR decline with a reduced risk of eGFR decline in high-dose aspirin users with well-preserved renal function. However, the long-term effects of analgesia use on eGFR decline remain to be determined.