Reducing Expectations for Antibiotics in Patients With Upper Respiratory Tract Infections: A Primary Care Randomized Controlled Trial.

PURPOSE: Many family practitioners prescribe antibiotics for patients with upper respiratory tract infections (URTIs) to meet patients' expectations. We evaluated the impact of providing brief tablet-based information about antibiotic treatment of URTIs on patients' expectations for antibiotics and on family practitioners' antibiotic-prescribing behavior. METHODS: We performed a 3-arm randomized controlled trial among patients presenting with URTIs at 2 urban family practices in Auckland, New Zealand, during winter 2018. Participants were randomly allocated to view a presentation about the futility of antibiotic treatment of URTIs, the adverse effects associated with antibiotics, or the benefits of healthy diet and exercise (active control), immediately before their consultation. Before and after viewing the presentations, participants used a Likert scale to rate the strength of their belief that antibiotics are effective for treating URTIs and of their desire to be prescribed an antibiotic. Patients reported whether an antibiotic had been prescribed, and pharmacy dispensing records were reviewed to determine whether an antibiotic was dispensed. RESULTS: Participants who viewed either the futility or the adverse effects presentation had greater reductions in their expectations to receive antibiotics than the control group. The mean reduction (95% CI) was 1.1 (0.8-1.3) for the futility group, 0.7 (0.4-0.9) for the adverse effects group, and 0.1 (0-0.3) for the control group (Cohen d = 0.7; P <.001). There was no significant difference among the 3 groups with regard to antibiotic prescribing (P = .84) or dispensing (P = .43). CONCLUSIONS: A brief tablet-based waiting room intervention significantly reduced participants' expectations about receiving antibiotics for URTI immediately before their family practitioner consultation. The intervention did not influence family practitioner prescribing behavior, however.

A Comprehensive Study on Self-Assembly and Gelation of C13-Dipeptides-From Design Strategies to Functionalities.

Computational and experimental methods were applied to investigate the self-assembly and gelation of C13-dipeptides. A modified aggregation propensity (APS) was introduced to correlate the effects of side chains of amino acids on the tendency to aggregate. From the experimental results, the ranges of 0.156 < APS < 0.250 seemed to be a proper region for the C13-dipeptides to form hydrogels, while other molecules with higher or lower APS were insoluble or dissociated. As observed from molecular dynamics simulations, the C13-dipeptides first formed small aggregates through hydrophobic interactions and then rearranged through electrostatic attractions and hydrogen bonds for self-assembly. The C13-dipeptides tended to be antiparallel packed, as shown by hydrogen bonding analyses. Experimental observations and analyses on the structures of C13-dipeptide hydrogels matched the computational conclusions very well. From the five selected gelators, i.e., C13-GW, C13-VY, and C13-WT, strong π-π stacking was observed. For C13-WS, strong hydrogen bonding was found, and in C13-WY, both strong π-π interactions and hydrogen bonds were found. It takes around 90 min or longer for C13-dipeptides to form hydrogels, and those formed by C13-WY and C13-WS had weak water holding capacities, which might be due to strong intermolecular hydrogen bonding. From rheological studies, the C13-dipeptides formed strong chemical gels that were stabilized by strong interactions between the molecular aggregates. These gelators exhibit the potentials to be environmentally friendly substitutes for the common functionalized peptide gelators.

Coassembly of C13-Dipeptides: Gelations from Solutions and Precipitations.

C13-dipeptides that did not gel on their own were found to form hydrogels when combined with mixtures (coassembly). At pH = 4.6, by mixing negatively charged C13-WD (C13-WD2- and/or C13-WD-) with C13-KW or C13-YK, where the side chain of K carried positive charge, two composite hydrogels with different mechanical properties were formed. The gels exhibited various fiber structures that would account for their individual functionalities. According to molecular dynamics computer simulations, the composite systems formed spherical micelles through hydrophobic interactions that further aggregate to form gels through electrostatic interactions. The electrostatic repulsions between C13-WD molecules were interfered by insertions of C13-KW or C13-YK molecules, which result in gel formation in the composite systems. The results of computer simulations well explained the experimental observations, which provided new insights into the design and selection strategies for peptide gelators.

Associations between compulsory community treatment and continuity of care in a three year follow-up of the Oxford Community Treatment Order Trial (OCTET) cohort.

BACKGROUND: Most studies investigating the effectiveness of Community Treatment Orders (CTOs) use readmission to hospital as the primary outcome. Another aim of introducing CTOs was to improve continuity of care. Our study was a 3-year prospective follow-up which tested for associations between CTOs and continuity of care. METHODS: Our study sample included 333 patients recruited to the Oxford Community Treatment Order Trial (OCTET). We collected data on continuity of care using eight previously operationalized measures. We analysed the association between CTOs and continuity of care in two ways. First, we tested the association between continuity of care and OCTET randomisation arm (CTO versus voluntary care via Section 17 leave). Second, we analysed continuity of care and CTO exposure independent of randomisation; using any exposure to CTO, number of days on CTO, and proportion of outpatient days on CTO as outcomes. RESULTS: 197 (61%) patients were made subject to CTO during the 36-month follow-up. Randomisation to CTO arm was significantly associated with having a higher proportion of clinical documents copied to the user but no other measures of continuity. Having a higher proportion of outpatient days on CTO (irrespective of randomisation) was associated with fewer 60 day breaks without community contact. A sensitivity analysis found that any exposure to CTO and a higher proportion of outpatient days on CTO were associated with fewer days between community mental health team contacts and 60 day breaks without contact. CONCLUSION: We found some evidence of an association between CTO use and better engagement with the community team in terms of increased contact and fewer breaks in care. Those with CTO experience had a higher number of inpatient admissions which may have acted as a mediator of this association. We found limited evidence for an association between CTO use and other measures of continuity of care.

The association between continuity of care and readmission to hospital in patients with severe psychosis.

PURPOSE: Providing good continuity of care to patients is considered a vital component of community mental health services, but there is limited evidence that it is associated with good outcomes. We measured service use and a multidimensional concept of continuity of care in 323 patients who were to be discharged from hospital following compulsory treatment for psychosis to investigate the association between continuity and rehospitalisation. METHODS: We conducted a 36-month prospective cohort study of the patients recruited to the Oxford Community Treatment Order Trial (OCTET). We collected data from medical records on eight previously operationalized measures of continuity. We conducted regression analyses to determine the association between these measures and readmission to hospital, time to readmission, and the number of days spent in hospital. RESULTS: Almost two thirds (n = 206, 63.8%) of patients were readmitted. Patients were seen frequently, with a mean of 2.9 (SD = 2.47) contacts a month throughout the follow-up. Less frequent contact was significantly associated with lower odds of rehospitalisation and fewer days in hospital. More changes in the patient's care coordinator were associated with more time in hospital. Patients who had a higher proportion of clinical correspondence copied to them spent fewer days in hospital. CONCLUSION: Patients with severe and relapsing psychotic illness are seen frequently and consistently in community mental health services. Higher levels of patient contact could be a response to the severity of illness rather than a marker of quality of care. Using a simple linear interpretation of contact frequency as a measure of continuity of care in this patient group may be of limited value in modern services.

Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/ß-catenin complex.

The evolution of cadherins, which are essential for metazoan multicellularity and restricted to metazoans and their closest relatives, has special relevance for understanding metazoan origins. To reconstruct the ancestry and evolution of cadherin gene families, we analyzed the genomes of the choanoflagellate Salpingoeca rosetta, the unicellular outgroup of choanoflagellates and metazoans Capsaspora owczarzaki, and a draft genome assembly from the homoscleromorph sponge Oscarella carmela. Our finding of a cadherin gene in C. owczarzaki reveals that cadherins predate the divergence of the C. owczarzaki, choanoflagellate, and metazoan lineages. Data from these analyses also suggest that the last common ancestor of metazoans and choanoflagellates contained representatives of at least three cadherin families, lefftyrin, coherin, and hedgling. Additionally, we find that an O. carmela classical cadherin has predicted structural features that, in bilaterian classical cadherins, facilitate binding to the cytoplasmic protein ß-catenin and, thereby, promote cadherin-mediated cell adhesion. In contrast with premetazoan cadherin families (i.e., those conserved between choanoflagellates and metazoans), the later appearance of classical cadherins coincides with metazoan origins.

The use of megaprosthesis in the treatment of periprosthetic knee fractures.

PURPOSE: The optimum treatment for periprosthetic fractures in the region of the distal femur is undefined. Although internal fixation for prostheses which are stable is commonly utilised, this can lead to very prolonged morbidity and failure of the fracture to unite. Where the prosthesis is either loose or infected, revision surgery is required and a 'tumour type' prosthesis can be successfully utilised. METHODS: The outcome of 27 patients treated by an endoprosthetic replacement for periprosthetic fracture of the distal femur between 1988 and 2013 are reported. Two cases were treated by two-stage revision due to persistent infection. Clinical outcomes were assessed by Knee Society score and Knee Society pain scores. RESULTS: All 27 patients mobilised rapidly in the post-operative period and infection where present was eradicated by the technique. There have been no cases of further revision in the patients where clinical follow-up is available. Knee Society scores following treatment averaged 88 and pain scores 43 at six months post-operatively. Eight patients have died during the long study period reflecting the age of the study population. CONCLUSIONS: The use of a tumour-type endoprosthesis in situations of comminuted periprosthetic fractures associated with a loose prosthesis shows favourable results with low complication rates and rapid mobilisation.

Web-based emergency department patient satisfaction surveys may introduce potential for bias.

BACKGROUND: Emergency departments (ED) have proposed utilizing a Web-based format to distribute patient satisfaction surveys, but the potential for bias in this distribution method has not been assessed. OBJECTIVE: The aim of this study was to evaluate the characteristics of ED patients who have access to the Internet to better understand potential bias in Web-based patient satisfaction surveys. METHODS: We distributed a 20-question survey to consenting, English-speaking adult patients presenting to the ED from December 2010 to March 2012. Patients reported demographic information and answered questions related to their access and use of the Internet. RESULTS: Seven hundred four patients participated in the study; 90% of Whites reported Internet access, vs. 82% of Hispanics (p = 0.034). Ninety-two percent of patients with at least some college education had Internet access, compared to 79% of those with a high school education level or lower (p ≤ 0.001). Of households reporting an income of > $22,000/year, 95% had Internet access, compared to 77% of those reporting a household income < $22,000/year (p ≤ 0.001). Ninety-four percent of participants < 40 years of age had Internet access, compared to 83% between the ages of 40 and 56 years, and 77% for those over 56 years of age (p < 0.001). CONCLUSION: A Web-based distribution of ED patient satisfaction surveys may underrepresent minorities, patients without college education, those with lower income, and patients older than 40 years. This information may provide guidance in interpreting results of Web-based patient satisfaction surveys and may suggest the need for multiple sampling methods.

Newly postulated neurodevelopmental risks of pediatric anesthesia: theories that could rock our world.

PURPOSE: General anesthetics can induce apoptotic neurodegeneration and subsequent maladaptive behaviors in animals. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes. The relevance of animal data to clinical practice is unclear and to our knowledge the causality underlying observed associations in humans is unknown. We reviewed newly postulated neurodevelopmental risks of pediatric anesthesia and discuss implications for the surgical care of children. MATERIALS AND METHODS: We queried the MEDLINE®/PubMed® and EMBASE® databases for citations in English on pediatric anesthetic neurotoxicity with the focus on references from the last decade. RESULTS: Animal studies in rodents and primates demonstrate apoptotic neuropathology and subsequent maladaptive behaviors after exposure to all currently available general anesthetics with the possible exception of α2-adrenergic agonists. Similar adverse pathological and clinical effects occur after untreated pain. Anesthetic neurotoxicity in animals develops only after exposure above threshold doses and durations during a critical neurodevelopmental window of maximal synaptogenesis in the absence of concomitant painful stimuli. Anesthetic exposure outside this window or below threshold doses and durations shows no apparent neurotoxicity, while exposure in the context of concomitant painful stimuli is neuroprotective. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes, particularly after multiple exposures. The causality underlying the associations is unknown. Ongoing investigations may clarify the risks associated with current practice. CONCLUSIONS: Surgical care of all patients mandates appropriate anesthesia. Neurotoxic doses and the duration of anesthetic exposure in animals may have little relevance to clinical practice, particularly surgical anesthesia for perioperative pain. The causality underlying the observed associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes is unknown. Anesthetic exposure may be a marker of increased risk. Especially in young children, procedures requiring general anesthesia should be performed only as necessary and general anesthesia duration should be minimized. Alternatives to general anesthesia and the deferral of elective procedures beyond the first few years of life should be considered, as appropriate. Participation in ongoing efforts should be encouraged to generate further data.

Virtual Shadowing: An Effective Approach to Gaining Exposure to the Field of Emergency Medicine.

Purpose: Shadowing is an important part of medical student education. The COVID-19 pandemic limited medical students' hospital access. At the same time, virtual access to learning experiences has expanded greatly. In response, we implemented a novel virtual shadowing system to provide students with convenient and safe exposure to the Emergency Department (ED). Patients and Methods: Six EM faculty hosted 2-hour virtual shadowing for up to 10 students per experience. Students registered via signupgenius.com. Virtual shadowing was conducted using a HIPAA-compliant ZOOM account on an ED issued mobile telehealth Monitor/iPad. The physician would bring the iPad into the room, obtain consent from patients, and ensure students were able to see the encounter. Between visits, students were encouraged to ask questions using the chat function and microphone. A short de-briefing followed each shift. Each participant received a survey about the experience. The survey consisted of 4 questions for demographics, 9 Likert style questions to assess efficacy, and 2 free response sections for comments and feedback. All survey responses were anonymous. Results: In total, 58 students participated in 18 virtual shadowing sessions with an average of 3-4 students per session. Survey responses were collected between October 20, 2020 and November 20, 2020. The overall response rate was 96.6% (56/58 surveys completed). Of respondents, 46 (82.1%) rated the experience as "effective" or "very effective" at providing exposure to Emergency Medicine. Fifty-three (94.6%) said they would participate in virtual shadowing in the ED again, and 48 (85.7%) would do virtual shadowing in another specialty were it available. Conclusion: We found virtual shadowing to be an easy to implement and effective way for students to shadow physicians in the ED. Even in post-pandemic times, virtual shadowing should be explored as an accessible and effective way to expose students to a broad array of specialties.

Intranasal sufentanil for the treatment of acute pain in a winter resort clinic.

INTRODUCTION: Painful extremity injuries are common patient complaints in resort clinics, urgent care clinics, and emergency departments. We hypothesized that intranasal (IN) sufentanil could provide rapid, noninvasive, effective pain relief to patients presenting with acute extremity injuries. METHODS: This was an unblinded, nonrandomized, observational study that enrolled a convenience sample of patients presenting to a university-affiliated ski clinic with acute moderate to severe pain associated with a traumatic injury between the months of January and March 2011. Patients were excluded if they reported an allergy to sufentanil or had hypoxia, significant head injury, or hypotension. Nurses administered IN sufentanil using an IN atomizer device. The nurse recorded patient-reported pain scores (0-10 scale) on arrival and at 10, 20, and 30 minutes after administration of sufentanil. RESULTS: During the study period, 40 patients were enrolled; 75% were men. The average age was 32 years (range, 16-60 years). The average dose of sufentanil was 37.7 µg. Five patients (12.5%) were given additional IN analgesia. Average pain on arrival was 9 (on a 10-point scale), and the mean reduction in pain scores was 4.7 (95% confidence interval [CI], 3.67-5.57) at 10 minutes, 5.79 (95% CI, 4.81-6.77) at 20 minutes, and 5.74 (95% CI, 4.72-6.76) at 30 minutes. CONCLUSION: In this limited observational trial, IN sufentanil provided rapid, safe, and noninvasive pain relief to patients presenting with acute traumatic extremity injuries. Given the ease of administration, this may serve as a viable option for use in other settings, such as urgent care clinics and emergency departments.

Value of Environmental Health During the COVID-19 Pandemic: A Story From Indian Country.

The coronavirus disease 2019 (COVID-19) pandemic challenged not only the health-care industry, but also the public health infrastructure in new and wide-ranging ways. Environmental health (EH) professionals have proven to be an essential component of the interdisciplinary public health solution required to prevent, respond, and recover from the COVID-19 pandemic. The Indian Health Service's Division of Environmental Health Services is a community-based program offering a broad scope of environmental health services and technical assistance. Significant COVID-19 workload activities were recorded from March 2020 through March 2021. A total of 62.7% of the Division's federal staff completed a 24-question survey in February/March 2021. Primary roles relating to community-based EH, institutional EH, and incident command system support/teams became apparent. Results indicated Division of Environmental Health Services staff provided critical leadership and used their established, trusted, interdisciplinary partnerships to help ensure critical resources and services were available in Indian Country.

Public Health Measures to Address the Impact of Climate Change on Population Health-Proceedings from a Stakeholder Workshop.

BACKGROUND: The World Health Organization identified climate change as the 21st century's biggest health threat. This study aimed to identify the current knowledge base, evidence gaps, and implications for climate action and health policymaking to address the health impact of climate change, including in the most underserved groups. METHODS: The Horizon-funded project ENBEL ('Enhancing Belmont Research Action to support EU policy making on climate change and health') organised a workshop at the 2021-European Public Health conference. Following presentations of mitigation and adaptation strategies, seven international researchers and public health experts participated in a panel discussion linking climate change and health. Two researchers transcribed and thematically analysed the panel discussion recording. RESULTS: Four themes were identified: (1) 'Evidence is key' in leading the climate debate, (2) the need for 'messaging about health for policymaking and behaviour change' including health co-benefits of climate action, (3) existing 'inequalities between and within countries', and (4) 'insufficient resources and funding' to implement national health adaptation plans and facilitate evidence generation and climate action, particularly in vulnerable populations. CONCLUSION: More capacity is needed to monitor health effects and inequities, evaluate adaptation and mitigation interventions, address current under-representations of low- or middle-income countries, and translate research into effective policymaking.

A Novel Mouse Model to Analyze Non-Genomic ERα Physiological Actions.

Nongenomic effects of estrogen receptor α (ERα) signaling have been described for decades. Several distinct animal models have been generated previously to analyze the nongenomic ERα signaling (eg, membrane-only ER, and ERαC451A). However, the mechanisms and physiological processes resulting solely from nongenomic signaling are still poorly understood. Herein, we describe a novel mouse model for analyzing nongenomic ERα actions named H2NES knock-in (KI). H2NES ERα possesses a nuclear export signal (NES) in the hinge region of ERα protein resulting in exclusive cytoplasmic localization that involves only the nongenomic action but not nuclear genomic actions. We generated H2NESKI mice by homologous recombination method and have characterized the phenotypes. H2NESKI homozygote mice possess almost identical phenotypes with ERα null mice except for the vascular activity on reendothelialization. We conclude that ERα-mediated nongenomic estrogenic signaling alone is insufficient to control most estrogen-mediated endocrine physiological responses; however, there could be some physiological responses that are nongenomic action dominant. H2NESKI mice have been deposited in the repository at Jax (stock no. 032176). These mice should be useful for analyzing nongenomic estrogenic responses and could expand analysis along with other ERα mutant mice lacking membrane-bound ERα. We expect the H2NESKI mouse model to aid our understanding of ERα-mediated nongenomic physiological responses and serve as an in vivo model for evaluating the nongenomic action of various estrogenic agents.

Obesity-related cardiovascular risk factors after long- term resistance training and ginger supplementation.

Obesity and its metabolic consequences are major risk factors for cardiovascular morbidity and mortality. However, lifestyle interventions, including exercise training and dietary components may decrease cardiovascular risk. Hence, this study was conducted to assess the effects of ginger supplementation and progressive resistance training on some cardiovascular risk factors in obese men. In a randomized double-blind design, 32 obese Iranian men (BMI ≥ 30) were assigned in to one of four groups: Placebo (PL, n = 8); ginger group (GI, n = 8) that consumed 1 gr ginger/d for 10 wk; resistance training plus placebo (RTPL, n = 8); and 1gr ginger plus resistance exercise (RTGI, n = 8). Progressive resistance training was performed three days per week for 10 weeks and included eight exercises. At baseline and after 10 weeks, body composition and anthropometric indices were measured. To identify other risk factors, venous blood samples were obtained before and 48-72 hours after the last training session for measurement of blood lipids (LDL-C, HDL-C, TG), systemic inflammation (CRP), and insulin resistance (HOMA-IR). After 10 weeks both RTGI and RTPL groups showed significant decreases in waist circumference (WC), waist-to-hip ratio (WHR), body fat percent, body fat mass, total cholesterol, and insulin resistance (p < 0.05) and a significant increase in fat free mass (FFM) (p < 0.05), while it remained unchanged in PL and GI. Further, significant decreases in the mean values of CRP were observed in all groups except PL (p < 0.05). Our results reveal that resistance training is an effective therapeutic strategy to reduce cardiovascular risk in obese Iranian men. Further, ginger supplementation alone or in combination with resistance training, also reduces chronic inflammation. However more research on the efficacy of this supplement to reduce cardiovascular risk in humans is required. Key pointsLong- term resistance training reduced cardiovascular risk factors in obese men.Ginger supplementation can also decrease chronic low grade inflammation in obese men.More researches are warranted to elicit the effects of these interventions on cardiovascular risk factors in humans.

Impact of the introduction of falls risk assessment toolkit on falls prevention and psychotropic medicines' utilisation in Walsall: an interrupted time series analysis.

OBJECTIVE: To determine the impact of the introduction of a falls risk assessment toolkit (FRAT) in a UK medical centre on the number and cost of non-elective admissions for falls and psychotropic medication utilisation. DESIGN: Interrupted time series analysis quantifying the number and cost of non-elective admissions for falls and primary care use data for Rushall Medical Centre before and after the implementation of FRAT at July 2017. SETTING: Data on the monthly number and cost of non-elective admissions for falls and number of referrals and assessment to the falls service were provided by Walsall Clinical Commissioning Group. Primary care prescribing cost and volume data for Rushall Medical Centre was derived from the Openprescribing.net website for prescriptions dispensed between April 2015 and November 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The number and cost of non-elective admissions for falls and number of referrals and assessment to the falls service, and the volume of utilisation of psychotropic medicines. RESULTS: Following the implementation of FRAT at Rushall Medical Centre in July 2017, the number of non-elective admissions for falls decreased at a rate of 0.414 admissions per month (p<0.033, 95% CI -0.796 to -0.032). The utilisation of psychotropic medications (alimemazine, citalopram, escitalopram, fluoxetine, mirtazapine, olanzapine and risperidone) decreased. The expenditure on psychotropic medications prescribed/used at Rushall Medical Centre decreased by at least £986 per month (p<0.001, 95% CI -2067 to -986). CONCLUSIONS: The implementation of FRAT at Rushall Medical Centre was associated with a reduction in the number of non-elective admissions for falls. Assessment of these patients together with deprescribing of psychotropic medications resulted in a reduction in the number of non-elective admissions for falls and associated costs.

Effect of Silymarin and Quercetin in a Miniaturized Scaffold in Wistar Rats against Non-alcoholic Fatty Liver Disease.

Silymarin and quercetin (SQ) are known antioxidants with substantial free radical scavenging activities. The efficacy of SQ activity is restricted due to poor absorption and availability. This study aims to increase the hepatoprotective activity of SQ by a newer delivery technique. We have optimized a technique, miniaturized scaffold (MS), for the delivery of active compounds of SQ. SQ molecules were embedded in MS and characterized by morphology, particle size, miniaturization efficiency, and functional group. Further, the hepatoprotective effects of MSQ were investigated through in vitro and in vivo methods. Hepatotoxicity was induced in rats by carbon tetrachloride (CCl4), and subsequently, hepatotoxic rats were treated with the miniaturized scaffold of SQ (MSQ) for 8 weeks. The body weight were significantly high in groups fed with MSQ. A substantial decrease in triglyceride, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase activities were observed in rats treated with MSQ. Similarly, rats treated with MSQ exhibited lower lipid accumulation in the hepatocytes. The experiments clearly demonstrated the efficacy of MSQ as a superior hepatoprotective agent against non-alcoholic fatty liver disease simulated through toxicity induced by CCl4.

Improving uptake of Fracture Prevention drug treatments: a protocol for Development of a consultation intervention (iFraP-D).

INTRODUCTION: Prevention of fragility fractures, a source of significant economic and personal burden, is hindered by poor uptake of fracture prevention medicines. Enhancing communication of scientific evidence and elicitation of patient medication-related beliefs has the potential to increase patient commitment to treatment. The Improving uptake of Fracture Prevention drug treatments (iFraP) programme aims to develop and evaluate a theoretically informed, complex intervention consisting of a computerised web-based decision support tool, training package and information resources, to facilitate informed decision-making about fracture prevention treatment, with a long-term aim of improving informed treatment adherence. This protocol focuses on the iFraP Development (iFraP-D) work. METHODS AND ANALYSIS: The approach to iFraP-D is informed by the Medical Research Council complex intervention development and evaluation framework and the three-step implementation of change model. The context for the study is UK fracture liaison services (FLS), which enact secondary fracture prevention. An evidence synthesis of clinical guidelines and Delphi exercise will be conducted to identify content for the intervention. Focus groups with patients, FLS clinicians and general practitioners and a usual care survey will facilitate understanding of current practice, and investigate barriers and facilitators to change. Design of the iFraP intervention will be informed by decision aid development standards and theories of implementation, behaviour change, acceptability and medicines adherence. The principles of co-design will underpin all elements of the study through a dedicated iFraP community of practice including key stakeholders and patient advisory groups. In-practice testing of the prototype intervention will inform revisions ready for further testing in a subsequent pilot and feasibility randomised trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from North West-Greater Manchester West Research Ethics Committee (19/NW/0559). Dissemination and knowledge mobilisation will be facilitated through national bodies and networks, publications and presentations. TRIAL REGISTRATION NUMBER: researchregistry5041.

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. RESEARCH DESIGN AND METHODS: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. RESULTS: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. CONCLUSIONS: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Investigation of the milling-induced thermal behavior of crystalline and amorphous griseofulvin.

PURPOSE: To gain a better understanding of the physical state and the unusual thermal behavior of milled griseofulvin. METHODS: Griseofulvin crystals and amorphous melt quench samples were milled in a vibrating ball mill for different times and then analyzed using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Modulated DSC (mDSC) and annealing studies were done for the milled amorphous samples to further probe the effects of milling. RESULTS: Milling of griseofulvin crystals results in decrease in crystallinity and amorphization of the compound. A double peak is seen for crystallization in the DSC, which is also seen for the milled melt quench sample. Both enthalpy and temperature of crystallization decrease for the milled melt quenched sample. Tg is visible under the first peak with the mDSC, and annealing shows that increasing milling time results in faster crystallization upon storage. CONCLUSION: Milling of griseofulvin results in the formation of an amorphous form and not a mesophase. It increases the amount of surface created and the overall energy of the amorphous griseofulvin, which leads to a decreased temperature of crystallization. The two exotherms in the DSC are due to some particles having nuclei on the surface.