Can a mock medication-taking learning activity enable pharmacy students to experience the range of barriers and facilitators to medication adherence? An analysis informed by the Theoretical Domains Framework and COM-B model.

Background: Pharmacy professionals are well-placed to provide medication adherence support to patients. The Capability, Opportunity, Motivation-Behaviour (COM-B) and Theoretical Domains Framework (TDF) are two complementary models previously applied to medication-taking behaviour. Understanding the patient-specific barriers and facilitators to adherence using psychological frameworks from the early stages of pharmacy education enables the design and delivery of effective interventions. Objectives: To examine whether a novel 'mock medicine' learning activity enabled students to experience the range of barriers and facilitators to medication adherence using the COM-B and TDF. Methods: A mock medicine activity was conducted with students at pharmacy schools in three universities in the UK, Norway, and Australia over one week. Percentage adherence was calculated for five dosing regimens; theoretical framework analysis was applied to map reflective statements from student logs to COM-B and TDF. Results: A total of 349 students (52.6%) returned completed logs, with high overall mean adherence (83.5%, range 0-100%). Analysis of the 277 (79.4%) students who provided reflective statements included barriers and facilitators that mapped onto one (9%), two (29%) or all three (62%) of the COM-B components and all fourteen TDF domains (overall mean = 4.04; Uni 1 = 3.72; Uni 2 = 4.50; Uni 3 = 4.38; range 1-8). Most frequently mapped domains were 'Environmental context and resources' (n = 199; 72%), 'Skills' (n = 186; 67%), 'Memory, attention and decision-making' (184; 66%) and 'Beliefs about capabilities' (n = 175; 63%). Conclusions: This is the first study to utilise both COM-B and TDF to analyse a proxy measure of medication adherence in pharmacy education. Data mapping demonstrated that students experienced similar issues to patients when prescribed a short course of medication. Importantly, all the factors influencing medication-taking reported by students were captured by these two psychological frameworks. Future educational strategies will involve students in the mapping exercise to gain hands-on experience of using these psychological constructs in practice.

Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis.

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

The effect of visual interventions on illness beliefs and medication adherence for chronic conditions: A scoping review of the literature and mapping to behaviour change techniques (BCTs).

BACKGROUND: Maintaining health with chronic conditions often involves taking multiple medications; however, approximately 50% of patients with chronic conditions are non-adherent to medication. Patients' illness beliefs inform health behaviour, including medication-taking. Research has shown that visuals accompanying health information increased patient comprehension and the accuracy of illness perceptions. To date, the influence of visuals on illness beliefs and medication adherence has not been comprehensively reviewed. OBJECTIVES: The review aimed to collate available literature on visualisation interventions for illness beliefs and medication adherence in chronic conditions and identify key intervention characteristics. METHODS: A scoping review was conducted according to recommended guidelines and the PRISMA-ScR statement. Searches used keywords relating to 'illness', 'visual', 'adherence', 'illness perception', 'intervention', and 'medication'. Six databases were searched from inception to 2019; reference-list searching provided additional articles. Articles were included if the study population had a chronic health condition, the intervention included a visual element, had a measure of illness beliefs or medication adherence. Data regarding intervention characteristics and outcomes were extracted. Behaviour change techniques (BCTs) were identified to provide further insight into intervention characteristics. RESULTS: Initially, 18,012 articles were identified. Screening led to 293 full-text articles, ultimately resulting in 45 studies for final analysis. Forty-four were quantitative studies, 1 was qualitative. Studies were grouped into those using visuals to conceptualise a condition, medication reminders and educational interventions. Almost two-thirds of visual interventions were effective post-intervention, 3 sustained post-1-year, although many studies only assessed impact immediately post-intervention. BCTs from 'Natural consequences', 'Socialsupport' and 'Feedback and monitoring' categories were prevalent in effective interventions for both outcomes, particularly the 'Salience of consequences' BCT. CONCLUSIONS: This comprehensive scoping review found that visual interventions can positively influence illness beliefs and medication adherence. These findings highlight the need to further evaluate the impact and sustainability of visual interventions.

Ethnic and gender-specific incidence rates for hip fractures in South Africa: A multi-centre study.

BACKGROUND: Limited data exist on the incidence of hip fractures in South Africa (SA). We report gender and ethnic specific incidence rates of hip fractures in SA. METHODS: In a multicentre prospective study, conducted in geographically defined municipalities of three provinces in SA, a structured questionnaire was administered to all subjects aged 40 years and over, presenting with a new atraumatic hip fracture, from 1 April 2017 to 31 March 2018. Gender and ethnic specific incidence rates (IR) of hip fractures were calculated using population statistics from Statistics SA. FINDINGS: Of the 2767 subjects enrolled, 1914 (69·2%) were women and 853 (30·8%) were men. The majority of subjects were from the White population (40·9%) followed by those from the African (26·4%), Coloured (18·7%) and Indian (13·9%) populations. Men with hip fractures were significantly younger than women in the total group (69 [IQR 59-79] versus 77 years [IQR 68-84], p < 0·001) and in each ethnic group. White subjects were significantly older (p < 0·0001) and Africans significantly younger (p < 0·0001) than the other ethnic groups. In women, the highest IR was noted in the White population (176·0 per 100,000), followed by that in the Indian (147·7 per 100,000), Coloured (73·2 per 100,000) and African populations (43·6 per 100,000). A similar pattern was seen in men albeit at lower rates, with the highest rate in White men at 76·5 per 100,000. In the total study population and the African population, the IR was higher in men compared to women in subjects under 60 years. In the White population, the IR was higher in men compared to women in the 40-44 years age group. While in the Coloured and Indian populations the IR was higher in men compared to women in the 40-49 years and 45-54 years age groups, respectively. There was an increase in the relative risk ratios with age in the total study population, and in all ethnic groups in both women and men. INTERPRETATION: Hip fractures occur in all ethnic groups in South Africa with higher IRs in the White and Indian populations compared to the Coloured and African populations. Consistent with the published literature, the overall hip fracture IR was higher in women than in men, except in the younger age groups, and increased with age. FUNDING: South African Medical Research Council and the University of KwaZulu-Natal Competitive Research Grant.

Low cost CO2 sensing: A simple microcontroller approach with calibration and field use.

Understanding the spatial variability of gaseous carbon flux at a landscape scale requires intensive monitoring campaigns necessitating significant and perhaps prohibitive financial investment. Commercially available CO2 sensors may only partially fulfil the requirements of the researcher, thereby generating inadequate data. In this context we present the fully replicable designs for a low-cost, microcontroller-based gaseous CO2 concentration data logger suitable for field deployment at scale. It demonstrates a post-calibration accuracy of 96-99% and large onboard data storage for data collected at user-defined intervals. The sensor can be powered via USB or batteries, assembled by novice users, and produced for approximately £155. Post-calibration it was used to measure CO2 evasion from a peatland stream, environments known to be spatially and temporally variable CO2 sources, although potential applications are much wider in scope. The proliferation of low-cost, open-source, and user-made sensors in physical sciences could allow researchers to answer questions previously unanswerable due to the limitations of existing proprietary equipment. We encourage other research teams to use and adapt this design for a range of purposes and research questions beyond carbon processing in peatlands.

Dosimetric evaluation and beam characterization of pair production enhanced radiotherapy (PPER) with the use of organometallics.

The current study evaluates dosimetric and spectral effects when platinum (Pt)-based chemotherapeutics and less toxic tungstophosphoric-acid (TPA) organometallics are present during x-ray radiotherapy. We hypothesize that the use of high energy photon beams (i.e. 18 MV) will increase absorbed dose due to increased pair production from high-Z elements and thus result in additional tumor cell kill. EGSnrc code was used to examine the contribution of pair production to dose in the presence of the high-Z material (TPA, Pt mixtures and tungsten, W) as a function of beam energy. Variables included different concentrations (100 µmolar, 1 mmolar), depths (5 mm, 10 cm), thicknesses (5 mm, 5 cm) and energies (6, 18 MV). Overall, for the deeper depth, the 511 keV photon fluence increase was up 31% (18 MV-1 mmolar) while at 6 MV it was between 10%-11% depending on the concentration. For the shallower depth, 18 MV fluence increase was up 14.6% (1 mmolar) and 18.6% (1 mmolar) for the 6 MV. The dose enhancement effect due to pair production was up 25%-30% and a total 33%-58% depending on the depth. The benefit related to pair production was more for 18 MV and under conditions that simulated a realistic clinical setup. While part of the effect could be attributed to photoabsorption, a significant contribution of dose could result from pair production. Experimental clonogenic survival assay was consistent with the theory in that the low dose shoulder region of a cell survival curve was reduced using TPA and 18 MV compared with TPA and 6 MV or compared with no TPA and 18 MV; RBE was approximately 2 at the dose commonly used in conventional fractionated clinical radiotherapy. This suggests a potential new strategy for dose enhancement based on pair production using higher energy beamlines.

High levels of socioeconomic deprivation do not inhibit patients' communication of concerns in head and neck cancer review clinics.

To examine associations between socioeconomic status and the extent to which patients with cancer of the head and neck expressed concerns to surgeons during routine follow-up clinics, we analysed audio recordings of 110 consultations with one consultant. We used the Verona Coding Definitions of Emotional Sequences (VRCoDES) to measure communication between the doctor and the patient, and grouped the English indices of multiple deprivation (IMD) 2015 scores into deciles to compare the VRCoDES with socioeconomic status. There were no significant correlations between IMD decile and the number and type of cues and concerns, or the type of response by the consultant, but there was a positive correlation between IMD decile and duration of appointment (r=0.288, p<0.01). When the duration of appointment was controlled for, there was a negative correlation between IMD decile and number of cues and concerns (r=-0.221, p<0.05). These findings question the assumption that socioeconomic status is associated with a patient's willingness to express concerns. Shorter consultations suggest that less time is spent responding to their concerns or building a rapport. Clinicians might find it advantageous to adopt strategies that will improve their understanding of these patients and help them to communicate more effectively.

Two-year patient-reported outcomes following treatment of uveal melanoma.

PurposeTreatment of uveal melanoma can impair patients' psychological well-being. We evaluated patient-reported outcome measures (PROMs) of anxiety, depression, and quality of life (QoL) over 2 years following treatment in a consecutive sample of uveal melanoma patients, compared observations to population normative values and examined whether outcomes differed according to patients' age, gender, and whether or not they were treated by enucleation or had a poor prognosis (presence of monosomy 3).DesignProspective longitudinal study.ParticipantsPatients (N=411) with uveal melanoma treated between 2008 and 2011.MethodsSelf-report questionnaire study. We compared mean PROMs scores obtained 6 months, 1 year, and 2 years after treatment to published population normative values using 2-sample t-tests, and tested the association of these scores with gender, age, treatment by enucleation, and monosomy 3 using mixed-model ANOVAs.ResultsOn QoL and depression, patients were similar to or better than normative values at all time points, but there was some evidence that females were more anxious than female normative values (Ps<0.001-<0.05). Younger patients (P<0.01) and female patients (P<0.01) were the most anxious overall. Enucleation was not associated with PROMs. Patients with monosomy 3 showed more depressed mood at all the three time points (P<0.05).ConclusionsPatients treated for uveal melanoma can expect, within 6 months of treatment, to have a QoL that is similar to that of the general population. Younger female patients and patients with monosomy 3 are more likely to be distressed, and clinicians will need to be alert to this.

The use of diet diaries in general dental practice in England.

OBJECTIVES: Diet diaries are recommended as a tool to support behaviour change in dental patients at high risk of dental diseases. However, little is known about their use in dental practice. This study aimed to investigate whether and how general dental practitioners (GDPs) use diet diaries and identify factors which influence their use. METHODS: A postal questionnaire was sent to a stratified random sample of general dental practitioners. The questionnaire asked about demographic and professional characteristics of the GDPs and their practices regarding diet advice, collection of dietary information, diet diaries usage (e.g. frequency, considerations and barriers), and interpretation of diet diaries. Descriptive, bivariate and multivariate analyses were conducted. RESULTS: From 972 eligible GDP participants, 250 (26%) responses were received. Whilst almost all of these GDPs reported giving diet advice to patients routinely, and 40% reported also referring to dental care professionals in the practice to deliver dietary advice, only 28% (70) reported that they are involved in using diet diaries. GDPs appeared to target patients for dietary advice: GDPs reported they personally gave diet advice to an estimated 63% of their patients, and referred patients to DCPs for diet advice for 11% of their (GDPs') patients. GDPs used diet diaries more often for child than adult patients. Diet diaries usage was lower among younger dentists and in practices with higher percentages of NHS patients (p⟨0.05). Perceived insufficient remuneration for time involved in using diet diaries was the main reason given for their lack of use. CONCLUSION: Although recommended as best practice, most English GDPs do not frequently use diet diaries to collect diet information in dental practice, mainly due to perceived financial and time constraints. Development of a more efficient tool to assess the dietary habits of dental patients is needed.

Endovascular Repair of Ruptured Popliteal Artery Aneurysms: A Case Report and Review of the Literature.

OBJECTIVE/BACKGROUND: The objectives were to report the management and outcomes of a 96-year-old man who presented with an acutely swollen right leg due to a ruptured popliteal aneurysm, and to review the relevant literature. METHODS: A ruptured popliteal artery aneurysm is a rare diagnosis and is one that is often missed at time of presentation. Previous case reports have documented successful outcomes following surgical repair, and a smaller number following endovascular repair. This is a case report of a 96-year-old man who eventually underwent endovascular repair of a ruptured popliteal artery aneurysm after a delay in diagnosis. A literature review was performed to analyse published data in this field. RESULTS: The patient underwent an uncomplicated endovascular repair with a GORE® VIABAHN® stent. A 15-week follow-up ultrasound demonstrated biphasic flow in a patent stent-graft with an unchanged aneurysm sac size and no evidence of an endoleak. A review of the literature demonstrated nine cases of ruptured non-mycotic popliteal artery aneurysms treated endovascularly. Seven cases survived the postoperative period, three had no follow-up recorded, and four cases had patent stent-grafts at time of follow-up. CONCLUSION: Safe and effective endovascular repair of a ruptured popliteal artery aneurysm with endograft patency seen at the 15-week follow-up is reported. Review of the literature suggests that open repair remains the first-line management choice; however, endovascular repair is a valuable alternative. There is a further need for longer-term monitoring of endograft patency following endovascular repair.

Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning.

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days -16 and -15, fludarabine 30 mg/m(2) per day on day -7 through -3, IV busulfan 130 mg/m(2) per day on days -4 and -3 and cyclophosphamide 1500 mg/m(2) on day -2. rATG levels were therapeutic in all patients on day -14, but were sub-therapeutic (<1 µg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.

The safety of osteoporosis medication.

Osteoporosis is a common, costly and serious disease, which is still too often regarded as an inevitable part of the normal ageing process and therefore sub-optimally treated, especially in the elderly--in fact, only two out of every 10 patients who sustain a hip fracture receive any form of assessment or prophylactic therapy for osteoporosis. One out of five patients die within 1 year after a hip fracture, and < 50% are capable of leading an independent life. Yet very effective anti-fracture therapy, capable of reducing fracture risk by 35 - 60%, is available. A number of publications have recently questioned the safety of drugs routinely used to treat patients with osteoporosis. This paper attempts to put the situation into perspective and expresses the National Osteoporosis Foundation of South Africa's view on the safety of these drugs. Their efficacy in preventing skeletal fractures and their cost-effectiveness are not addressed in any detail. The paper emphasises the fact that all osteoporosis medications have side-effects, some of which are potentially life-threatening.

Trajectories of loneliness during childhood and adolescence: predictors and health outcomes.

The present study employed latent growth mixture modeling to discern distinct trajectories of loneliness using data collected at 2-year intervals from age 7-17 years (N = 586) and examine whether measures taken at age 5 years were good predictors of group membership. Four loneliness trajectory classes were identified: (1) low stable (37% of the sample), (2) moderate decliners (23%), (3) moderate increasers (18%), and (4) relatively high stable (22%). Predictors at age 5 years for the high stable trajectory were low trust beliefs, low trusting, low peer acceptance, parent reported negative reactivity, an internalizing attribution style, low self-worth, and passivity during observed play. The model also included outcome variables. We found that both the high stable and moderate increasing trajectories were associated with depressive symptoms, a higher frequency of visits to the doctor, and lower perceived general health at age 17. We discuss implications of findings for future empirical work.

Risk, worry and cosmesis in decision-making for contralateral risk-reducing mastectomy: analysis of 60 consecutive cases in a specialist breast unit.

INTRODUCTION: Although controversial, use of contralateral risk-reducing mastectomy (CRRM) is increasing. It is not clear whether reduction of objective breast cancer risk or other factors determine decisions for CRRM. We aimed to identify factors that influence these decisions by scrutinising how decisions were made in one centre. METHODS: We reviewed a consecutive series of 60 patients considered for CRRM in one centre. Data sources, analysed using qualitative methods, were records of routine psychological assessment, surgeon letters, case-notes and interviews with four surgeons. RESULTS: Perceptions of objective risk did not generally drive patients' requests or surgeons' decisions. Instead, CRRM appeared to be mainly performed for psychological reasons: to reduce patients' cancer worry and to achieve cosmetic benefits. CONCLUSION: Routine use of the term 'risk-reducing' surgery masks a clinical decision which usually reflects influences other than risk. As CRRM is often carried out for psychological reasons it follows that evidence about its psychosocial outcomes is needed.

Phenomenological model of interstitial fluid pressure in a solid tumor.

Tumor interstitial fluid pressure (TIFP) has the potential to predict tumor response to nonsurgical cancer treatments, including radiation therapy. At present the only quantitative measures available are of limited use, since they are invasive and yield only point measurements. We present the mathematical framework for a quantitative, noninvasive measure of TIFP. The model describes the distribution of interstitial fluid pressure in three distinct tumor regions: vascularized tumor rim, central tumor region, and normal tissue. A relationship between the TIFP and the fluid flow velocity at the periphery of a tumor is presented. This model suggests that a measure of fluid flow rate from a tumor into normal tissue reflects TIFP. We demonstrate that the acquisition of serial images of a tumor after the injection of a contrast agent can provide a noninvasive and potentially quantitative measure of TIFP.

Neoplasia in the chimpanzee (Pan spp.).

BACKGROUND: Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research. METHODS: Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically. RESULTS: In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males,and seven in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and two were undetermined. Neoplasia was most common in the urogenital system in females. CONCLUSIONS: Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.

Impact of Early Spring Weather Factors on the Risk of Tomato Spotted Wilt in Peanut.

Peanut growers in the southeastern United States have suffered significant economic losses due to spotted wilt caused by Tomato spotted wilt virus (TSWV). The virus is transmitted by western flower thrips, Frankliniella occidentalis, and tobacco thrips, F. fusca, and was first reported in the southeast in 1986. The severity of this disease is extremely variable in individual peanut fields, perhaps due to the sensitivity of the vector population to changing weather patterns. The objective of this study was to investigate the impact of early spring weather on spotted wilt risk in peanut. On-farm surveys of spotted wilt severity were conducted in Georgia peanut fields in 1998, 1999, 2002, 2004, and 2005. The percent spotted wilt intensity (%) for cv. Georgia Green was recorded and categorized into three intensity levels: low, moderate, and high. Meteorological data were obtained from the Georgia Automated Environmental Monitoring Network for the period between March 1 and April 30. Statistical analysis was conducted to identify weather variables that had significant impact on spotted wilt intensity. The results indicated a high probability of spotted wilt if the number of rain days during March was greater than or equal to 10 days and planting was before 11 May or after 5 June. The total evapotranspiration in April (>127 mm) and the average daily minimum temperature in March (>6.8°C) similarly increased the risk of spotted wilt. Knowing in advance the level of spotted wilt risk expected in a peanut field could assist growers with evaluating management options and significantly improve the impact of their decisions against spotted wilt risk in peanut.

A predictive model for spotted wilt epidemics in peanut based on local weather conditions and the tomato spotted wilt virus risk index.

Tomato spotted wilt virus (TSWV), a member of the genus Tospovirus (family Bunyaviridae), is an important plant virus that causes severe damage to peanut (Arachis hypogaea) in the southeastern United States. Disease severity has been extremely variable in individual fields in Georgia, due to several factors including variability in weather patterns. A TSWV risk index has been developed by the University of Georgia to aid peanut growers with the assessment and avoidance of high risk situations. This study was conducted to examine the relationship between weather parameters and spotted wilt severity in peanut, and to develop a predictive model that integrates localized weather information into the risk index. On-farm survey data collected during 1999, 2002, 2004, and 2005 growing seasons, and derived weather variables during the same years were analyzed using nonlinear and multiple regression analyses. Meteorological data were obtained from the Georgia Automated Environmental Monitoring Network. The best model explained 61% of the variation in spotted wilt severity (square root transformed) as a function of the interactions between the TSWV risk index, the average daily temperature in April (TavA), the average daily minimum temperature between March and April (TminMA), the accumulated rainfall in March (RainfallM), the accumulated rainfall in April (RainfallA), the number of rain days in April (RainDayA), evapotranspiration in April (EVTA), and the number of days from 1 January to the planting date (JulianDay). Integrating this weather-based model with the TSWV risk index may help peanut growers more effectively manage tomato spotted wilt disease.

Efficacy of suicide gene therapy in hypoxic rat 9L glioma cells.

Viral vector mediated suicide gene therapy (SGT) involving thymidine kinase (TK) or cytosine deaminase (CD) have considerable promise in the treatment of malignant brain tumors. An unresolved issue is to what extent tumor hypoxia influences the outcome of SGT since brain tumors characterized by regions of hypoxia have potentially reduced cellular metabolism and SGT's cytotoxicity is manifest through cellular metabolism. We studied in vitro and in vivo, the effect of hypoxia on the cytotoxicity of SGT in rat 9L glioma cells. Neither acute nor chronic hypoxia affected the cell killing of SGT by TK or CD. In vivo confirmation that SGT efficacy was not adversely affected by tumor hypoxia using the hypoxic cell marker pimonidazole was shown by the absence of a change in tumor hypoxia by SGT. These studies support the use of SGT utilizing either TK or CD gene strategies even when tumors are characterized by a hypoxic microenvironment.