Analysis of the profile, characteristics, patient experience and community value of community hospitals : a multimethod study

Background: Community hospitals have been part of England’s health-care landscape since the mid-nineteenth century. Evidence on them has not kept pace with their development. Aim: To provide a comprehensive analysis of the profile, characteristics, patient experience and community value of community hospitals. Design: A multimethod study with three phases. Phase one involved national mapping and the construction of a new database of community hospitals through data set reconciliation and verification. Phase two involved nine case studies, including interviews and focus groups with patients (n = 60), carers (n = 28), staff (n = 132), volunteers (n = 68), community stakeholders (n = 74) and managers and commissioners (n = 9). Phase three involved analysis of Charity Commission data on voluntary support. Setting: Community hospitals in England. Results: The study identified 296 community hospitals with beds in England. Typically, the hospitals were small (<30 beds), in rural communities, led by doctors/general practitioners (GPs) and nurses, without 24/7 on-site medical cover, providing step-down and step-up inpatient care, with an average length of stay of <30 days and a variable range of intermediate care services. Key to patients’ and carers’ experiences of community hospitals was their closeness to ‘home’ through their physical location, environment and atmosphere and the relationships that they support; their provision of personalised, holistic care; and their role in supporting patients through difficult psychological transitions. Communities engage with and support their hospitals through giving time (average = 24 volunteers), raising money (median voluntary income = £15,632), providing services (voluntary and community groups) and giving voice (e.g. communication and consultation). This can contribute to hospital utilisation and sustainability, patient experience, staff morale and volunteer well-being. Engagement varies between and within communities and over time. Community hospitals are important community assets, representing direct and indirect value: instrumental (e.g. health care), economic (e.g. employment), human (e.g. skills development), social (e.g. networks), cultural (e.g. identity and belonging) and symbolic (e.g. vitality and security). Value varies depending on place and time. Limitations: There were limitations to the secondary data available for mapping community hospitals and tracking charitable funds and to our sample of case study respondents, which concentrated on people with a connection to the hospitals. Conclusions: Community hospitals are diverse but are united by a set of common characteristics. Patients and carers experience community hospitals as qualitatively different from other settings. Their accounts highlight the importance of considering the functional, interpersonal, social and psychological dimensions of experience. Community hospitals are highly valued by their local communities, as demonstrated through their active involvement as volunteers and donors. Community hospitals enable the provision of local intermediate care services, delivered through an embedded, relational model of care, which generates deep feelings of reassurance. However, current developments, including the withdrawal of GPs, shifts towards step-down care for non-local patients and changing configurations of services, providers and ownership may undermine this. Future work: Comparative studies of patient experience in different settings, longitudinal studies of community support and value, studies into the implications of changes in community hospital function, GP involvement, provider-mix and ownership and international comparative studies could all be undertaken

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni.

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

NKp46+ natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection

Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12Rβ2+ ILC1, ST2+ ILC2 and NKp46+ natural killer (NK) innate lymphoid cell population expansions during Brugia malayi experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46+ NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+ ILC2 failed to expand. NKp46+ NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+ NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult B. malayi infection. This data was recapitulated using an Onchocerca ochengi male worm peritoneal implant model. When NKp46+ NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of B. malayi infection, susceptibility to adult B. malayi infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adult B. malayi infection followed by challenge infection leads to resistance against early larval B. malayi establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+ NK cells express markers of memory-like/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+ NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation

Generalized Dynamic Analysis of Structural Single Rocking Walls (SRWs)

The investigation of structural single rocking walls (SRWs) continues to gain interest as they produce self-centering lateral load responses with reduced structural damage. The Simple Rocking Model (SRM) with modifications has been shown to capture these responses accurately if the SRW and its underlying base are infinitely rigid. This paper advances previous rocking models by accounting for: 1) the inelastic actions at or near the base of the SRW; and 2) the flexural responses within the wall. Included in the proposed advancements are hysteretic and inherent viscous damping associated with these two deformation components so that the total dynamic responses of SRWs can be captured with good accuracy. A system of nonlinear equations of motion is developed, in which the rocking base is discretized into fibers using a zero-length element to locate the associated compressive deformations and damage. The flexural deformations of the rocking body are captured using an elastic term, while the impact events are modeled using impulse-momentum equations. Comparisons with experiments of structural precast concrete and masonry SRWs show that the proposed approach accurately estimates the dynamic responses of different SRWs with and without unbonded posttensioning, for various dynamic excitations and degrees of hysteretic action. Using the proposed approach, a numerical investigation employs different configurations of structural SRWs to quantify the various sources of energy loss, including hysteretic action and impact damping, during various horizontal ground motions

Effective Caspase Inhibition Blocks Neutrophil Apoptosis and Reveals Mcl-1 as Both a Regulator and a Target of Neutrophil Caspase Activation

Human tissue inflammation is terminated, at least in part, by the death of inflammatory neutrophils by apoptosis. The regulation of this process is therefore key to understanding and manipulating inflammation resolution. Previous data have suggested that the short-lived pro-survival Bcl-2 family protein, Mcl-1, is instrumental in determining neutrophil lifespan. However, Mcl-1 can be cleaved following caspase activity, and the possibility therefore remains that the observed fall in Mcl-1 levels is due to caspase activity downstream of caspase activation, rather than being a key event initiating apoptosis in human neutrophils

Dietary fructose in relation to blood pressure and serum uric acid in adolescent boys and girls

Evidence that fructose intake may modify blood pressure is generally limited to adult populations. This study examined cross-sectional associations between dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents aged 13–15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. Energy-adjusted fructose intake was derived from 3-day food records, serum uric acid concentration was assessed using fasting blood and resting blood pressure was determined using repeated oscillometric readings. In multivariate linear regression models, we did not see a significant association between fructose and blood pressure in boys or girls. In boys, fructose intake was independently associated with serum uric acid (P<0.01), and serum uric acid was independently associated with systolic blood pressure (P<0.01) and mean arterial pressure (P<0.001). Although there are independent associations, there is no direct relationship between fructose intake and blood pressure. Our data suggest that gender may influence these relationships in adolescence, with significant associations observed more frequently in boys than girls

Visualizing the 3D Architecture of Multiple Erythrocytes Infected with Plasmodium at Nanoscale by Focused Ion Beam-Scanning Electron Microscopy

Different methods for three-dimensional visualization of biological structures have been developed and extensively applied by different research groups. In the field of electron microscopy, a new technique that has emerged is the use of a focused ion beam and scanning electron microscopy for 3D reconstruction at nanoscale resolution. The higher extent of volume that can be reconstructed with this instrument represent one of the main benefits of this technique, which can provide statistically relevant 3D morphometrical data. As the life cycle of Plasmodium species is a process that involves several structurally complex developmental stages that are responsible for a series of modifications in the erythrocyte surface and cytoplasm, a high number of features within the parasites and the host cells has to be sampled for the correct interpretation of their 3D organization. Here, we used FIB-SEM to visualize the 3D architecture of multiple erythrocytes infected with Plasmodium chabaudi and analyzed their morphometrical parameters in a 3D space. We analyzed and quantified alterations on the host cells, such as the variety of shapes and sizes of their membrane profiles and parasite internal structures such as a polymorphic organization of hemoglobin-filled tubules. The results show the complex 3D organization of Plasmodium and infected erythrocyte, and demonstrate the contribution of FIB-SEM for the obtainment of statistical data for an accurate interpretation of complex biological structures