Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life: results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease.

OBJECTIVES: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. METHODS: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. RESULTS: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). CONCLUSION: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

Continuous and on-demand prescription increase in proton pump inhibitor consumption equally in real-world settings and did not result in different outcomes.Reaching a sufficient dose of proton pump inhibitor to reduce reflux symptom burden improves quality of life in patients with gastroesophageal reflux disease.

Quantifying the production of plant pollen at the farm scale.

Plant pollen is rich in protein, sterols and lipids, providing crucial nutrition for many pollinators. However, we know very little about the quantity, quality and timing of pollen availability in real landscapes, limiting our ability to improve food supply for pollinators. We quantify the floral longevity and pollen production of a whole plant community for the first time, enabling us to calculate daily pollen availability. We combine these data with floral abundance and nectar measures from UK farmland to quantify pollen and nectar production at the landscape scale throughout the year. Pollen and nectar production were significantly correlated at the floral unit, and landscape level. The species providing the highest quantity of pollen on farmland were Salix spp. (38%), Filipendula ulmaria (14%), Rubus fruticosus (10%) and Taraxacum officinale (9%). Hedgerows were the most pollen-rich habitats, but permanent pasture provided the majority of pollen at the landscape scale, because of its large area. Pollen and nectar were closely associated in their phenology, with both peaking in late April, before declining steeply in June and remaining low throughout the year. Our data provide a starting point for including pollen in floral resource assessments and ensuring the nutritional requirements of pollinators are met in farmland landscapes.

Predicting profiles of post-trauma adaptation in first responders and civilians after the 2013 Boston Marathon bombings: The role of distress, growth, and emotion regulation.

INTRODUCTION: Responses to trauma are often characterized either by the presence or absence of psychological distress; however, the process of adapting after trauma also includes potential positive change. While some studies document that the majority of individuals exposed to single event terrorism report low levels of psychological distress, more research is needed to understand different adaptation profiles following this type of trauma, and the factors that might predict responses. METHODS: We examined post-trauma responses in 257 first responders/medical professionals (66.8 percent) and civilians (33.2 percent) exposed to the 2013 Boston Marathon Bombings. Data for post-trauma profiles-post-traumatic growth (PTG), post-traumatic stress, and emotion regulation-and profile predictors-trauma proximity, trauma history, and coping flexibility-were collected approximately 2.5 years after the bombings. Latent profile analysis identified response profiles, and multinomial logistic regression identified demographic, event-specific, and psychological predictors of profile membership. RESULTS: Four profiles emerged: (1) symptomatic, (2) resistant, (3) resilient, and (4) struggling growth. First responder role decreased the odds of belonging to the struggling growth profile, as compared to the symptomatic profile. Greater coping flexibility and adaptive emotion regulation increased the odds of membership in the struggling growth, rather than symptomatic profile. CONCLUSION: A subset of individuals experiencing post-traumatic stress symptoms years after trauma exposure may also be utilizing flexible, adaptive coping strategies and experiencing PTG. First responders may have difficulty experiencing simultaneous -distress and growth, and interventions designed to promote healthy post-trauma adaptation for this population could be tailored accordingly.

Environmental and nutritional assessment of young children's diets in Norway: comparing the current diet with national dietary guidelines and the EAT-Lancet reference diet.

PURPOSE: Introducing healthy and sustainable diets early in life can promote lifelong healthy dietary patterns with a low environmental impact. Therefore, we aimed to estimate the environmental and nutritional consequences of a dietary change for 2-year-old children in Norway towards healthier dietary patterns. METHODS: Environmental impacts of the current habitual diet among 2-year-olds (n = 1413) were estimated for six impact categories and compared with scenario diets based on the Norwegian food-based dietary guidelines (FBDG) and the EAT-Lancet Commission reference diet. Last, we evaluated the nutritional adequacy of the diets against the Norwegian nutrition recommendations for children aged 2-5 years. The current diet was assessed by an FFQ. RESULTS: Environmental impacts of the current habitual diet were up to two times higher than those of the scenario diets. Compared with the current diet, impacts from the FBDG scenario diet were reduced by 35% for water use and 18% for terrestrial acidification, whereas impacts from the EAT-Lancet scenario diet were reduced by 51% for water use, 57% for terrestrial acidification, 36% for global warming potential and 27% for freshwater eutrophication. Milk and dairy products were the main contributors to environmental impacts in both the current diet and the FBDG scenario diet. The scenario diets were nutritionally adequate and improved the dietary quality among Norwegian 2-year-olds. CONCLUSION: Compared to current diets among young children, more plant-based dietary patterns in line with national FBDG or the EAT-Lancet Commission reference diet can improve the nutritional adequacy of diets and simultaneously reduce environmental impacts.

The relationship of socio-demographic factors and patient attitudes to connected health technologies: A survey of stroke survivors.

More evidence is needed on technology implementation for remote monitoring and self-management across the various settings relevant to chronic conditions. This paper describes the findings of a survey designed to explore the relevance of socio-demographic factors to attitudes towards connected health technologies in a community of patients. Stroke survivors living in the UK were invited to answer questions about themselves and about their attitudes to a prototype remote monitoring and self-management app developed around their preferences. Eighty (80) responses were received and analysed, with limitations and results presented in full. Socio-demographic factors were not found to be associated with variations in participants' willingness to use the system and attitudes to data sharing. Individuals' levels of interest in relevant technology was suggested as a more important determinant of attitudes. These observations run against the grain of most relevant literature to date, and tend to underline the importance of prioritising patient-centred participatory research in efforts to advance connected health technologies.

"Practice makes perfect" strategy for teaching aseptic techniques improved observational scores but not preparation potency.

INTRODUCTION: Student-compounded sterile preparations have been evaluated using observational scores, sterility testing, and potency determinations. Observational scores and potency determinations can be evaluated simultaneously, and three studies have been published using these assessment tools. One study found a significant number of students could not compound an acceptably potent preparation despite receiving very good observational scores. The previous study was judged to have an inferior instructional flaw, so a new teaching design, a "practice makes perfect" model, was utilized and was expected to increase the number of students compounding acceptably potent preparations. METHODS: The "practice makes perfect" method provided students with more practice and one-on-one instruction time in aseptic techniques. First-year pharmacy students received both group practice sessions and individualized instruction on six occasions interspersed between three compounding assessments. Observational scores and potency results were compared between this study and the previously published study. RESULTS: The "practice makes perfect" strategy improved students' observational scores but showed inconsistent results in the percentage of students who compounded an acceptably potent preparation and in the potency of preparations compounded by all students. There was no correlation between observational scores and potency values or between observational scores and the percentage of students compounding acceptably potent preparations at each individual observational score. CONCLUSIONS: The study demonstrated that there was either a systematic error in the analytical potency protocol or that the observations made during student compounding were not adequate to identify problems that led to poor potency.

Topical and Oral Therapies for Childhood Atopic Dermatitis and Plaque Psoriasis.

BACKGROUND: Treatment of atopic dermatitis and psoriasis in children is difficult due to lack of standardized treatment guidelines and few FDA-approved treatment options. Treatments approved for adults may be used off-label in pediatric patients. OBJECTIVE: This review evaluates the topical and oral treatment options available, including off-label uses, and provides a basic therapeutic guideline for pediatric atopic dermatitis and psoriasis. METHODS: A PubMed review of topical and systemic treatments for pediatric psoriasis and atopic dermatitis with information regarding age, efficacy, dosing, contra-indications, adverse events, and off-label treatments. RESULTS: The search identified seven topical and five systemic treatments that are routinely employed to treat pediatric atopic dermatitis and psoriasis. LIMITATIONS: Standardized guidelines regarding treatment choice, dosing, and long-term safety are scarce. Reviews may be subject to ascertainment bias. CONCLUSIONS: Current treatment guidelines are based on clinical experience and expert advice with few treatments officially approved for atopic dermatitis and psoriasis in children.

Pain perception in Parkinson's disease: A systematic review and meta-analysis of experimental studies.

While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson's disease (PD), experimental research is equivocal and mechanisms are poorly understood. We conducted a meta-analysis of studies comparing PD patients to healthy controls (HCs) in their response to experimental pain stimuli. Articles were acquired through systematic searches of major databases from inception until 10/2016. Twenty-six studies met inclusion criteria, comprising 1292 participants (PD=739, HCs=553). Random effects meta-analysis of standardized mean differences (SMD) revealed lower pain threshold (indicating hyperalgesia) in PD patients during unmedicated OFF states (SMD=0.51) which was attenuated during dopamine-medicated ON states (SMD=0.23), but unaffected by age, PD duration or PD severity. Analysis of 6 studies employing suprathreshold stimulation paradigms indicated greater pain in PD patients, just failing to reach significance (SMD=0.30, p=0.06). These findings (a) support the existence of hyperalgesia in PD, which could contribute to the onset/intensity of clinical pain, and (b) implicate dopamine deficiency as a potential underlying mechanism, which may present opportunities for the development of novel analgesic strategies.

A collaborative approach to improving patient access in general practice: impact of three different pilot schemes in 12 general practices in Greenwich.

BACKGROUND: With rising patient demand and expectations, many practices are struggling to respond to the demand for appointments. OBJECTIVE: To investigate different approaches to improving access to general practice and assess the impact on (i) patient experience, (ii) practice staff experience and (iii) activity in A&E and walk-in centres. METHOD: Greenwich CCG piloted three approaches in 12 volunteer practices. The schemes were:(1) Systematic GP telephone triage of all appointment requests.(2) Analysis and comparison of practice data including demand and capacity to identify opportunities for improvement.(3) Online consultations. Qualitative and quantitative evaluation was undertaken. RESULTS: Overall results were inconclusive and no one pilot scheme was overwhelmingly successful in improving patient experience of access or reducing practice workload. Scheme 1 telephone triage: In some cases, overall demand on clinician time through the day reduced as face-to-face consultations were replaced with shorter telephone consultations. However, in other practices, total consulting time went up when telephone consultations took longer than the suggested average 5 min. Scheme 2 practice analysis and benchmarking: The pilot practices implemented no significant changes. Scheme 3 online consultations: Take up was low, with users as a percentage of total list size dropping significantly to even lower levels in the second half of the pilot - from 3.13% in the first three months to 1.20% in the second three months. CONCLUSION: As the pilots did not improve the overall patient experience of access or practice workload, the pilot schemes were not rolled out by the CCG. From the CCG's point of view, it was valuable to test out the effect of a scheme before committing further resources.

Bisphosphonates and evidence for association with esophageal and gastric cancer: a systematic review and meta-analysis.

OBJECTIVES: Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of epidemiological studies have been published with conflicting results. We conducted a systematic review and meta-analysis of observational studies, to determine the risk of esophageal and gastric cancer in users of bisphosphonates compared with non-users. DESIGN: We searched PubMed, MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating bisphosphonates and esophageal or gastric cancer. We calculated pooled ORs and 95% CIs for the risk of esophageal or gastric cancer in bisphosphonate users compared with non-users. We performed a sensitivity analysis of alendronate as this was the most common single drug studied and is also the most widely used in clinical practice. RESULTS: 11 studies (from 10 papers) examining bisphosphonate exposure and UGI cancer (gastric and esophageal), met our inclusion criteria. All studies were retrospective, 6/11 (55%) case-control and 5/11(45%) cohort, and carried out using data from 5 longitudinal clinical databases. Combining 5 studies (1 from each database), we found no increased risk, OR 1.11 (95% CI 0.97 to 1.27) of esophageal cancer in bisphosphonate users compared with non-users and no increased risk of gastric cancer in bisphosphonate users, OR 0.96 (95% CI 0.82 to 1.12). CONCLUSION: This is the fourth and most detailed meta-analysis on this topic. We have not identified any compelling evidence for a significantly raised risk of esophageal cancer or gastric cancer in male and female patients prescribed bisphosphonates.

An evidence-based referral management system: insights from a pilot study.

OBJECTIVES: Improving the informational quality of referrals from primary to secondary care and appropriately re-directing referrals is an important goal of clinical commissioning groups in England. Based on the available empirical evidence, a referral management and booking service that combined referral guidelines, online referral templates and administrative and clinical triage, was developed by a primary care trust in southeast London. METHODS: A pilot study of 13 out of 46 practices in the trust was conducted using a mixed methods approach. Referral numbers were investigated by analysing changes in practices' rates of first outpatient attendances in secondary care. Informational referral quality was assessed by analysing triage outcomes. Semi-structured interviews were used to inquire about practices' evaluation of the new system. Structured telephone interviews were conducted to assess patients' satisfaction. RESULTS: Overall rates of first outpatient attendances declined more strongly for pilot practices than controls. The number of referrals challenged for being incomplete or having insufficient clinical information decreased. The rate of referrals challenged by clinical triage for not conforming to referral guidelines was well below the rate of inappropriate referrals published in the literature. Interviews with practices revealed a number of themes and a broad range of attitudes. Patients were highly satisfied. DISCUSSION: Findings provided favourable evidence for the effectiveness of the new referral management system. They were, however, preliminary. If referrals into secondary care continued to be reduced on a long-term basis, the system would be cost effective despite the time and effort required for clinical triage.

Early diagnostic suggestions improve accuracy of GPs: a randomised controlled trial using computer-simulated patients.

BACKGROUND: Designers of computerised diagnostic support systems (CDSSs) expect physicians to notice when they need advice and enter into the CDSS all information that they have gathered about the patient. The poor use of CDSSs and the tendency not to follow advice once a leading diagnosis emerges would question this expectation. AIM: To determine whether providing GPs with diagnoses to consider before they start testing hypotheses improves accuracy. DESIGN AND SETTING: Mixed factorial design, where 297 GPs diagnosed nine patient cases, differing in difficulty, in one of three experimental conditions: control, early support, or late support. METHOD: Data were collected over the internet. After reading some initial information about the patient and the reason for encounter, GPs requested further information for diagnosis and management. Those receiving early support were shown a list of possible diagnoses before gathering further information. In late support, GPs first gave a diagnosis and were then shown which other diagnoses they could still not discount. RESULTS: Early support significantly improved diagnostic accuracy over control (odds ratio [OR] 1.31; 95% confidence interval [95%CI] = 1.03 to 1.66, P = 0.027), while late support did not (OR 1.10; 95% CI = 0.88 to 1.37). An absolute improvement of 6% with early support was obtained. There was no significant interaction with case difficulty and no effect of GP experience on accuracy. No differences in information search were detected between experimental conditions. CONCLUSION: Reminding GPs of diagnoses to consider before they start testing hypotheses can improve diagnostic accuracy irrespective of case difficulty, without lengthening information search.

Autocrine VEGF signaling promotes proliferation of neoplastic Barrett's epithelial cells through a PLC-dependent pathway.

BACKGROUND & AIMS: Tumor cells express vascular endothelial growth factor (VEGF), which induces angiogenesis. VEGF also activates VEGF receptors (VEGFRs) on or within tumor cells to promote their proliferation in an autocrine fashion. We studied the mechanisms of autocrine VEGF signaling in Barrett's esophagus cells. METHODS: Using Barrett's epithelial cell lines, we measured VEGF and VEGFR messenger RNA and protein, and studied the effects of VEGF signaling on cell proliferation and VEGF secretion. We studied the effects of inhibiting factors in this pathway on levels of phosphorylated phospholipase Cγ1 (PLCG1), protein kinase C, and extracellular signal-regulated kinases (ERK)1/2. We performed immunohistochemical analysis of phosphorylated VEGFR2 on esophageal adenocarcinoma tissues. We studied effects of sunitinib, a VEGFR2 inhibitor, on proliferation of neoplastic cells and growth of xenograft tumors in mice. RESULTS: Neoplastic and non-neoplastic Barrett's cells expressed VEGF and VEGFR2 messenger RNA and protein, with higher levels in neoplastic cells. Incubation with recombinant human VEGF significantly increased secretion of VEGF protein and cell number; knockdown of PLCG1 markedly reduced the recombinant human VEGF-stimulated increase in levels of phosphorylated PLCG1 and phosphorylated ERK1/2 in neoplastic cells. Esophageal adenocarcinoma tissues showed immunostaining for phosphorylated VEGFR2. Sunitinib inhibited VEGF signaling in neoplastic cells and reduced weight and volume of xenograft tumors in mice. CONCLUSIONS: Neoplastic and non-neoplastic Barrett's epithelial cells have autocrine VEGF signaling. In neoplastic Barrett's cells, VEGF activation of VEGFR2 initiates a PLCG1-protein kinase C-ERK pathway that promotes proliferation and is self-sustaining (by causing more VEGF production). Strategies to reduce autocrine VEGF signaling (eg, with sunitinib) might be used to prevent or treat cancer in patients with Barrett's esophagus.

Bisphosphonates and risk of upper gastrointestinal cancer--a case control study using the General Practice Research Database (GPRD).

BACKGROUND: Concerns have been raised as to the safety of bisphosphonates; in particular a possible link between bisphosphonate use and upper gastrointestinal (GI) cancer. Two published studies using different study populations but drawn from earlier versions of the same national UK database, reached differing conclusions: one finding no evidence for an increase in the risk of gastric or oesophageal cancer in bisphosphonate users and one finding a small but significantly increased risk of oesophageal cancer linked to duration of bisphosphonate use. METHODOLOGY/ PRINCIPAL FINDINGS: Design-A case control study comparing bisphosphonate prescribing in cases of upper GI cancer from 1995 to 2007 using UK primary care electronic health records (GPRD). Main Outcome Measure-Relative Risk (approximated to Odds Ratio for rare events) for oesophageal and gastric cancer development in bisphosphonate users compared to non-users. The odds of being a case of oesophageal cancer, adjusted for smoking status, were significantly increased in women who had had one or more bisphosphonate prescriptions, odds ratio 1.54 (95% CI 1.27-1.88) compared to non-users. There was no significant effect on gastric cancer in women, odds ratio adjusted for smoking status, 1.06 (95% CI 0.83-1.37) and also no apparent risk in men for either oesophageal or gastric cancer, odds ratio adjusted for smoking status 0.78 (95%CI 0.56-1.09) and 0.87 (95% CI 0.55-1.36) respectively. CONCLUSIONS/ SIGNIFICANCE: Our results support a small but significant increased risk of oesophageal cancer in women prescribed bisphosphonates and is based on the largest number of exposed cases to date in the UK.

Long-term effects from a randomized trial of two public health preventive interventions for parental depression.

This article presents long-term effects of a randomized trial evaluating 2 standardized, manual-based prevention strategies for families with parental mood disorder: informational lectures and a brief, clinician-based approach including child assessment and a family meeting. A sample of 105 families, in which at least 1 parent suffered from a mood disorder and at least 1 nondepressed child was within the 8- to 15-year age range, was recruited. Parents and children were assessed separately at baseline and every 9 to 12 months thereafter on behavioral functioning, psychopathology, and response to intervention. Both interventions produced sustained effects through the 6th assessment point, approximately 4.5 years after enrollment, with relatively small sample loss of families (<14%). Clinician-based families had significantly more gains in parental child-related behaviors and attitudes and in child-reported understanding of parental disorder. Child and parent family functioning increased for both groups and internalizing symptoms decreased for both groups, with no significant group differences. These findings demonstrate that brief, family-centered preventive interventions for parental depression may contribute to long-term, sustained improvements in family functioning.