Perspectives of pharmacists about collaborative asthma care model in primary care

BackgroundThe newly recognized General Practice Pharmacist (GPP) model in Australia, where non-dispensing pharmacists work in collaboration with general practitioners (primary care physicians) within their general practice/clinics represent an efficient yet novel approach for the management of chronic diseases. In chronic conditions, such as asthma, these models can help achieve optimal health outcomes, given current gaps between guidelines and practice.ObjectiveThe aim of this study was to elicit pharmacists’ views and recommendations about pragmatic models of collaboration between GPPs and general practitioners in providing asthma management services in future service delivery models.MethodsCommunity pharmacists were recruited via convenience sampling and passive snowballing techniques. Qualitative, semi-structured, in-depth interviews were conducted. Recorded interviews were transcribed verbatim and analyzed utilizing NVivo® 11 software. Obtained data were content analyzed for emergent themes using the Braun and Clarke framework.ResultsTwenty-five interviews were conducted. Asthma management challenges in current practice and the implementation practicality of asthma care GPP models comprised the two major emerging themes. Pharmacists' time and workload constraints and patients' reluctance to seek pharmacists’ assistance to dispel misconceptions about asthma control were reported to be major barriers for the implementation of optimal asthma management services in community pharmacy. While a GPP dependent on several criteria. The development of specified channels for inter-professional communication for sharing of patient information and the willingness of stakeholders to accept and access such a model were reported. Funding and remuneration were considered critical factors by most participants. The professional self-autonomy of each healthcare professional involved in the GPP model was also highlighted as pertinent issue.ConclusionsThis study provides significant insights to create pragmatic scalable versions of a GPP care model that could facilitate better asthma care after key barriers and facilitators identified by participants are carefully addressed.     

Short breath-hold, volumetric coronary MR angiography employing steady-state free precession in conjunction with parallel imaging.

An ECG-gated, 3D steady-state free precession (SSFP) technique in conjunction with sensitivity encoding (SENSE)-based parallel imaging was implemented for short breath-hold, volumetric coronary MR angiograpy (CMRA). Two parallel imaging acquisition strategies (employing 1 R-R and 2 R-R intervals, respectively) were developed to achieve 1) very short breath-hold times (12 s for a heart rate of 60 bpm), and 2) small acquisition windows to minimize sensitivity to physiologic motion. Both strategies were examined in CMRA applications over a range of heart rates. A four-point scale blinded reading (with 4 indicating the most desirable features) revealed substantial image quality improvements for the accelerated data as compared to the nonaccelerated approach. The 1 R-R interval scheme yielded an image score of 3.39 +/- 0.60, and was found to be particularly suitable for low heart rates (P = 0.0008). The 2 R-R interval strategy yielded an image score of 3.35 +/- 0.64, and was more appropriate for higher heart rates (P = 0.03). The results demonstrate that 3D SSFP combined with parallel imaging is a versatile method for short breath-hold CMRA while maintaining high spatial resolution. This strategy permits imaging of the major coronary artery distributions in two to three breath-holds using targeted slabs, and offers the potential for single breath-hold, large-volume CMRA.     

Reverse culture shock,distress symptoms and psychological well-being of fresh foreign degree holders in Pakistan

This study explored to what extent does reverse culture shock predict the level of anxiety, depression, and psychological well-being among fresh foreign degree holders in Pakistan, in addition to finding out the relationship between the study variables. Participants consisted of 124 fresh foreign degree holders (109 men and 15 women) who were recruited through purposive and snowball sampling techniques. Reverse Culture Shock Scale, Major Depression Inventory, Beck Anxiety Inventory, and WHO-5 Well-being Index were used to measure study variables. Results show that reverse culture shock is a strong predictor of psychological well-being explaining 23% variance in well-being scores of fresh foreign degree holders. As hypothesized, it has positive associations with distress symptoms including anxiety and depression, whereas, a negative correlation was found with psychological well-being and the age of fresh foreign degree holders. However, contrary to the hypothesis, reverse culture shock has no association with time passed since arrival back home and duration of stay abroad.     

Identification and characterisation of common glow-worm RNA viruses

Virus Genes - The common glow-worms (Lampyris noctiluca) are best known for emission of green light by their larvae and sexually active adult females. However, both their DNA and RNA viruses remain...     

Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens

A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 °C and 62.7 °C, respectively) and predominantly native-like, as determined by negative-stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1.Vaccines have successfully stopped or limited infections by preventing pathogen transmission and have thereby contributed toward eradication of deadly diseases (1). Nonetheless, successful vaccination against highly variable pathogens, such as enveloped RNA viruses, remains a daunting task. For example, vaccination against influenza virus is only modestly effective because constant antigenic drift necessitates yearly updates of the vaccine (2). HIV (HIV-1) is also an RNA virus with a high mutation rate that creates extensive sequence diversity and facilitates immune evasion (3, 4). During HIV-1 infection, immune responses are often narrowly focused against a small subset of viruses (5). The development of broadly neutralizing antibodies (bnAbs) is relatively rare (5–15% of infections), and usually only arises after antigenic stimulation by constantly evolving viral variants over the course of 1–3 y or longer (6, 7). A vaccine that confers protection against the global diversity of HIV-1 is highly challenging and, as yet, an unachieved goal (8).Neutralizing antibodies (nAbs) are a correlate of protection for almost all successful vaccines (9, 10). The envelope glycoprotein (Env) is the only HIV-1–encoded surface protein and, as such, constitutes the sole bnAb target. A major problem in vaccine development is the intrinsic metastability of Env that is essential for its membrane-fusion function (11). To mediate cell entry, the Env trimer must undergo a series of complex, receptor-triggered conformational changes within and between its noncovalently associated subunits, gp120 and gp41, to progress from prefusion to fusion-active to postfusion forms (12). How to create stable recombinant Env proteins in a prefusion conformation relevant for bnAb recognition and elicitation has been an area of intensive research.We have previously described a cleaved, stabilized Env trimer from a clade A isolate, termed BG505 SOSIP.664 (13). This SOSIP trimer represents the paradigm for display of all known bNAb epitopes (except the membrane proximal external region, MPER, which was omitted due to its hydrophobicity), with minimal exposure of most non-nAb epitopes (14–16). This BG505 trimer has been extensively characterized and validated structurally in complexes with at least one member of each main bnAb class [trimer apex, PG9 (13); N332-epitope, PGT122 (17, 18); CD4 binding site, PGV04 (19); and cleaved gp41/gp120 interface, PGT151 (20)]. This Env trimer was recently shown to elicit strong, but narrow, nAb responses in animals against the autologous, neutralization-resistant (tier-2) virus (21).It is unlikely that the BG505 SOSIP.664 trimer by itself will achieve the goal of inducing bnAbs against heterologous tier-2 viruses (21). That task may be beyond the capabilities of any single Env protein. One possible strategy to drive a broader response is to use a diverse set of trimers derived from different HIV-1 isolates/clades, analogous to the trivalent/tetravalent seasonal influenza vaccines. The challenge an HIV vaccine faces is much more onerous, however, because of the far greater global sequence diversity of HIV-1 (3).We recently described the production and in vitro characterization of another native-like trimer, B41 SOSIP.664 (clade B) (16) to complement its clade A counterpart. As an immunogen, the B41 trimer also generated a strong, but narrow, tier-2 autologous nAb response (21). Here, we sought to identify additional trimers with comparable properties but based on clade C sequences. Clade C is responsible for over 50% of all new infections worldwide, predominantly in sub-Saharan Africa—the epicenter of the AIDS pandemic (22). Neutralization profiles of clade C viruses suggest their trimers may differ subtly from other clades. For example, despite possessing all putative N-linked glycans associated with the 2G12 epitope, many clade C viruses are resistant to this bnAb (23). Thus, clade C trimers may have atypical structural or glycosylation properties.Here, we screened a panel of 15 clade C env sequences to seek SOSIP.664 trimers with high yield, good thermal stability, native-like antigenicity (display of bnAb epitopes, occlusion of non-nAb epitopes), and native-like structure. We found two trimers, DU422 and ZM197M, with these desired properties. Cryo-electron microscopy (cryo-EM) of ZM197M SOSIP.664 in complex with VRC01 Fab confirmed that the trimers are native-like and provided valuable insights into the distinct neutralization profiles of clade C viruses. These high-quality clade C trimers can now contribute to vaccine strategies aimed at inducing a bnAb response.     

A comparison between two different immobilization devices for radiation therapy treatment of pelvic cancer using VMAT

ObjectivesTo assess setup reproducibility of low kneefix with feetfix (LKF-FF) system and its operator-reported convenience by reference to low dual leg positioner (LDLP), among patients treated with pelvic radiotherapy.MethodsA retrospective controlled trial was carried out at the radiotherapy unit. It included patients who underwent radical radiotherapy to the pelvis using VMAT, and who benefitted from LDLP (N = 30) or LKF-FF (N = 30) immobilization system. Average absolute shifts (AAS) and total vector errors (TVE) were computed and compared between the two systems, using translational (lateral, longitudinal and vertical) and rotational (X, Y and Z planes) directions. Accuracy rates were computed on pooled data including 1529 VMAT images, 819 in LDLP and 710 in LKF-FF groups, using different cutoffs. Radiotherapists' subjective assessment of the device's ease of setup, handling, cleaning, and storage, and patient comfort was carried out comparatively between the two devices.ResultsNo statistically significant difference was observed between the two systems in systematic settings, while LKF-FF outperformed LDLP in random settings; notably in vertical translation and X and Z rotational shifts. Analysis of TVEs showed significant decrease in rotational TVE in LKF-FF group (mean=1.38° versus 2.38, p = 0.003) by reference to LDLP, respectively; however, both systems had comparable translational TVE (p = 0.590). In pooled analysis, LKF-FF enabled an overall increase in setup accuracy rates in rotational directions by up to 15% and 19% at ±1° and ±2° accuracy levels, respectively (p<0.05). Subjective assessments showed that the two immobilization systems were comparable regarding all investigated dimensions; however, the overall radiotherapists’ preference leaned toward LDLP.ConclusionThe newly implemented LKF-FF system outperformed LDLP in terms of setup reproducibility, notably in rotational directions, where it enhanced setup accuracy rates by up to 19%. Long-term use of LKF-FF may improve the users’ satisfaction.     

Efficacy of daily vs. weekly supplementation of iron in schoolchildren with low iron status

Iron deficiency anemia (IDA) is still a major nutritional and public health problem in developing countries. The prevalence among young children and pregnant women is particularly high. Daily oral supplementation with medicinal iron is considered an effective strategy for reducing the incidence of IDA but non-compliance is a major problem with this strategy. We undertook this study to compare the results of once-weekly vs. daily oral iron supplementation in schoolchildren. Sixty children ranging between 5 and 10 years with iron deficiency anemia were selected from a school in Karachi, Pakistan and were divided into two equal groups, i.e., daily and weekly supplementation groups. Hemoglobin (Hb), hematocrit (Hct), serum iron, total iron binding capacity (TIBC), and serum ferritin were determined before the start of the study. Ferrous sulfate (200 mg) was given daily to the daily supplementation group and once-weekly to the weekly supplementation group for 2 months. When post-supplementation values of the above-mentioned parameters were determined, a significant improvement was observed in all parameters in both groups. It is concluded that once-weekly iron supplementation is as effective as daily supplementation for the treatment of iron deficiency anemia. Moreover, weekly iron supplementation is cost effective and has no or fewer side-effects.