Primary care in the twenty-first century

Summary • The NHS remains one of the world’s better health care systems. But the proportion of the UK’s GDP allocated to health and social care is only about three quarters of that now spent by leading European nations. To meet changing needs health and social care providers in England must improve their capacity to offer convenient access to preventive and ‘common need’ diagnostic and treatment services to people of all ages, and also to provide well-coordinated social and health care to individuals at high risk of suffering avoidable episodes of serious illness and needlessly losing their independence. • If personal and public health is to be raised to the highest possible level improving primary health and health related social care – which together represent little more than a fifth of combined NHS and local authority social service outlays – is vital. Health care will in future move more towards professionally facilitated prevention and primary care supported self-care in the community, backed by the relatively infrequent use of highly specialised services supplied in hospitals. • The unique attributes of British general medical practice will allow it to serve as a central plank for continuing service development. The formation of local Health Federations and related primary care focused organisations could in future lend itself to holding single budgets for health and related social care along the lines proposed by advocates of the Primary Care Home approach to service improvement. This would offer significant gains for service users. Wherever cost effective, services ought to be ‘made’ by local care providers. Where necessary they should be purchased from other sources. • There is a large body of evidence indicating that Community Pharmacy can play an extended part in delivering accessible health care, alongside roles like reducing prescription errors and facilitating better medicines use. Increasing the number of clinical pharmacists working in GP practices is a valuable step. But it cannot substitute for a clear vision for the future of community pharmacies as ‘first contact’ health care providers. • If community pharmacists successfully extend their clinical care roles this would free general practice and linked community capacity to work towards reducing inappropriate hospital admissions and unduly long inpatient stays. Without well planned, pro-active, interventions pharmacy skills will be under-used and the established community pharmacy network lost. Yet if each community pharmacy in England were able to take on just 10 per cent of the average general practice’s existing workload over the next five years, this will release approaching 5,000 GPs and similar volumes of practice staff for additional service provision. • Responsibility for achieving more effective primary care working arrangements lies mainly with GPs, nurses, social workers and pharmacists themselves, because only they are in a position to adequately understand the tasks with which they are engaged and the detailed needs of the people they serve. However, individual professionals alone cannot transform the NHS. Excellent national leadership and appropriate funding and governance systems are also vital for nation-wide success. • Nine out of 10 people in England currently live within a 20 minute walk of a community pharmacy. Some planners may wish to see savings made via concentrating dispensing in warehouse-like facilities and increasing the use of medicines home delivery services. Yet at a system-wide level a potentially more desirable way forward could be to extend pharmacist prescribing and improve shared health record systems. This would combine convenient local medicines supply with more accessible forms of ‘pharmacist first’ care in areas ranging from managing blood pressure to providing better chronic obstructive pulmonary disease (COPD) and type 2 diabetes prevention and care. • The health and social care system in England has been affected by imbalances that are linked to the fact that social care is means tested while NHS care is free. This has created perverse incentives that may in the past have undermined services such as community nursing. Inadequate high level leadership also impairs service quality. But if health gain focused co-operative professional enterprise can be combined with well-informed decision making and robust national and local resource allocation strategies that effectively support the delivery of well-coordinated primary care, further improvements in individual and population health will be achieved

Towards developing a building typology for Sudan

Sudan suffers from hard summers with temperatures approaching 42 0C in the South and 48 0C in the North. In spite of that, the technical solutions in buildings for protection against solar radiation and natural ventilation are generally beyond reach. There isn’t sufficient information provided on the characteristics of the building stock, building physics and energy use of buildings in Sudan. The main objective of this research paper is to collect the data from the population and housing census, scientific research papers and different reports, and to use these in preparing a building typology table. The climate in Sudan is divided into three zones: warm desert climate, warm semi-arid climate, and tropical savanna climate zone. The building varies according to the climate zones, geographical feature, and urbanization levels. Building materials range from natural ones like straw, wood, and mud to moderns one like bricks and concrete. Building typology varies from structures to provide temporary shelter to the permanent single or multi-family houses. The main result of this research paper is to identify a building typology in Sudan with reference buildings. This is the first paper that introduced the typology table of Sudan

Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required

Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer.

INTRODUCTION: Tumors that express estrogen receptor alpha (ERα+) comprise 75% of breast cancers in women. While treatments directed against this receptor have successfully lowered mortality rates, many primary tumors initially or later exhibit resistance. The paucity of murine models of this luminal tumor subtype has hindered studies of factors that promote their pathogenesis and modulate responsiveness to estrogen-directed therapeutics. Since epidemiologic studies closely link prolactin and the development of ERα+ tumors in women, we examined characteristics of the aggressive ERα+ and ERα- carcinomas which develop in response to mammary prolactin in a murine transgenic model (neu-related lipocalin- prolactin (NRL-PRL)). To evaluate their relationship to clinical tumors, we determined phenotypic relationships among these carcinomas, other murine models of breast cancer, and features of luminal tumors in women. METHODS: We examined a panel of prolactin-induced tumors for characteristics relevant to clinical tumors: histotype, ERα/progesterone receptor (PR) expression and estrogen responsiveness, Activating Protein 1 (AP-1) components, and phosphorylation of signal transducer and activator of transcription 5 (Stat5), extracellular signal regulated kinase (ERK) 1/2 and AKT. We compared levels of transcripts in the ERα-associated luminal signature that defines this subtype of tumors in women and transcripts enriched in various mammary epithelial lineages to other well-studied genetically modified murine models of breast cancer. Finally, we used microarray analyses to compare prolactin-induced ERα+ and ERα- tumors, and examined responsiveness to estrogen and the anti-estrogen, Faslodex, in vivo. RESULTS: Prolactin-induced carcinomas were markedly diverse with respect to histotype, ERα/PR expression, and activated signaling cascades. They constituted a heterogeneous, but distinct group of murine mammary tumors, with molecular features of the luminal subtype of human breast cancer. In contrast to morphologically normal and hyperplastic structures in NRL-PRL females, carcinomas were insensitive to ERα-mediated signals. These tumors were distinct from mouse mammary tumor virus (MMTV)-neu tumors, and contained elevated transcripts for factors associated with luminal/alveolar expansion and differentiation, suggesting that they arose from physiologic targets of prolactin. These features were shared by ERα+ and ERα- tumors, suggesting a common origin, although the former exhibited transcript profiles reflecting greater differentiation. CONCLUSIONS: Our studies demonstrate that prolactin can promote diverse carcinomas in mice, many of which resemble luminal breast cancers, providing a novel experimental model to examine the pathogenesis, progression and treatment responsiveness of this tumor subtype

Strength Training for Arthritis Trial (START): design and rationale

Background Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. Methods/Design This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. Discussion Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact

Impact of pharmacy care upon adherence to cardiovascular medication a feasibility controlled trial

ABSTRACT Objective To investigate the feasibility and potential impact of a pharmacy care intervention, involving motivational interviews among patients with acute coronary syndrome, on adherence to medication and on health outcomes. Methods This article reports a prospective, interventional, controlled feasibility/pilot study. Seventy one patients discharged from a London Heart Attack Centre following acute treatment for a coronary event were enrolled and followed up for 6 months. Thirty two pharmacies from six London boroughs were allocated into intervention or control sites. The intervention was delivered by community pharmacists face-to-face in the pharmacy, or by telephone. Consultations were delivered as part of the New Medicine Service or a Medication Usage Review. They involved a 15–20 min motivational interview aimed at improving protective cardiovascular medicine taking. Results At 3 months, there was a statistically significant difference in adherence between the intervention group (M=7.7, SD=0.56) and the control group (M=7.0, SD=1.85), p=0.026. At 6 months, the equivalent figures were for the intervention group M=7.5, SD=1.47 and for the controls M=6.1, SD=2.09 (p=0.004). In addition, there was a statistically significant relationship between the level of adherence at 3 months and beliefs regarding medicines ( p=0.028). Patients who reported better adherence expressed positive beliefs regarding the necessity of taking their medicines. However, given the small sample size, no statistically significant outcome difference in terms of recorded blood pressure and low density lipoproteincholesterol was observed over the 6 months of the study. Conclusions The feasibility, acceptability and potentially positive clinical outcome of the intervention were demonstrated, long with a high level of patient acceptability. It had a significant impact on cardiovascular medicine taking adherence. But these findings must be interpreted with caution. The intervention should be tested in a larger trial to ascertain its full clinical utility

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

Studying the effect of shear stud distribution on the behavior of steel-reactive powder concrete composite beams using ABAQUS software

Using the ABAQUS software, this article presents a numerical investigation on the effects of various stud distributions on the behavior of composite beams. A total of 24 continuous 2-span composite beam samples with a span length of 1 m were examined (concrete slab at the top and steel I-section at the bottom). The concrete slab used is made of a reactive powder concrete with a compressive strength of 100.29 MPa. The total depth of each sample was 0.220 m. The samples were separated into four groups. The first group involved 6 specimens with shear connectors distributed into 2 rows with different distances (65, 85, 105, 150, 200, and 250 mm). The second group had the same spacing of shear connectors as the first group except that the shear connectors were distributed with one row along the longitudinal axis. The third group consisted of six specimens with single and double shear connectors distributed along the longitudinal axis. The fourth group included six specimens with one row of shear connectors arranged in a staggered distribution along the longitudinal axis. Results show that the optimum spacing was 105 mm in all groups and the deflection in group four fluctuated up and down due to the non-symmetrical distribution of the shear connectors

Improved accessibility of emergency obstetrics and newborn care (EmONC) services for maternal and newborn health: a community based project

Background: Every year an estimated three million neonates die globally and two hundred thousand of these deaths occur in Pakistan. Majority of these neonates die in rural areas of underdeveloped countries from preventable causes (infections, complications related to low birth weight and prematurity). Similarly about three hundred thousand mother died in 2010 and Pakistan is among ten countries where sixty percent burden of these deaths is concentrated. Maternal and neonatal mortality remain to be unacceptably high in Pakistan especially in rural areas where more than half of births occur. Method/Design: This community based cluster randomized controlled trial will evaluate the impact of an Emergency Obstetric and Newborn Care (EmONC) package in the intervention arm compared to standard of care in control arm. Perinatal and neonatal mortality are primary outcome measure for this trial. The trial will be implemented in 20 clusters (Union councils) of District Rahimyar Khan, Pakistan. The EmONC package consists of provision of maternal and neonatal health pack (clean delivery kit, emollient, chlorhexidine) for safe motherhood and newborn wellbeing and training of community level and facility based health care providers with emphasis on referral of complicated cases to nearest public health facilities and community mobilization. Discussion: Even though there is substantial evidence in support of effectiveness of various health interventions for improving maternal, neonatal and child health. Reduction in perinatal and neonatal mortality remains a big challenge in resource constrained and diverse countries like Pakistan and achieving MDG 4 and 5 appears to be a distant reality. A comprehensive package of community based low cost interventions along the continuum of care tailored according to the socio cultural environment coupled with existing health force capacity building may result in improving the maternal and neonatal outcomes. The findings of this proposed community based trial will provide sufficient evidence on feasibility, acceptability and effectiveness to the policy makers for replicating and scaling up the interventions within the health syste