Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium

How many is enough? Determining optimal count totals for ecological and palaeoecological studies of testate amoebae

Testate amoebae are increasingly used in ecological and palaeoecological studies of wetlands. To characterise the amoeba community a certain number of individuals need to be counted under the microscope. To date, most studies have aimed for 150 individuals, but that sample size is not based on adequate evidence. When testate amoeba concentrations are low, it can be difficult or impossible to reach this total. The impacts of lower count totals have never been seriously scrutinised. We investigated the impact of count size on number of taxa identified, quantitative inferences of environmental variables and the strength of the links between amoebae and environmental data in the context of predicting depth to water table. Low counts were simulated by random selection of individuals from four existing datasets. Results show progressively diminishing returns by all criteria as count size increases from low numbers to counts of 150. A higher count is required to identify all taxa than to adequately characterise the community for transfer function inference. We suggest that in most cases, it will be a more efficient use of time to count a greater number of samples to a lower count. While a count of 50 individuals may be sufficient for some samples from some sites we recommend that counts of 100 individuals should be sufficient for most samples. Counts need only be increased to 150 or more where the aim is to identify relatively minor, but still potentially ecologically relevant community changes. This approach will help reduce lack of replication and low resolution, which are common limitations in testate amoeba-based palaeoecological and ecological studies

Psychosocial interventions for patients with advanced cancer – a systematic review of the literature

Advanced cancer is associated with emotional distress, especially depression and feelings of sadness. To date, it is unclear which is the most effective way to address these problems. This review focuses on the effects of psychosocial interventions on the quality of life (QoL) of patients with advanced cancer. It was hypothesised that patients will benefit from psychosocial interventions by improving QoL, especially in the domain of emotional functioning. The review was conducted using systematic review methodology involving a systematic search of the literature published between 1990 and 2002, quality assessment of included studies, systematic data extraction and narrative data synthesis. In all, 10 randomised controlled studies involving 13 trials were included. Overall interventions and outcome measures across studies were heterogeneous. Outcome measures, pertaining to the QoL dimension of emotional functioning, were most frequently measured. A total of 12 trials evaluating behaviour therapy found positive effects on one or more indicators of QoL, for example, depression. The results of the review support recommendation of behaviour therapy in the care of patients with advanced cancer

Psychosocial interventions for patients with advanced cancer – a systematic review of the literature

Advanced cancer is associated with emotional distress, especially depression and feelings of sadness. To date, it is unclear which is the most effective way to address these problems. This review focuses on the effects of psychosocial interventions on the quality of life (QoL) of patients with advanced cancer. It was hypothesised that patients will benefit from psychosocial interventions by improving QoL, especially in the domain of emotional functioning. The review was conducted using systematic review methodology involving a systematic search of the literature published between 1990 and 2002, quality assessment of included studies, systematic data extraction and narrative data synthesis. In all, 10 randomised controlled studies involving 13 trials were included. Overall interventions and outcome measures across studies were heterogeneous. Outcome measures, pertaining to the QoL dimension of emotional functioning, were most frequently measured. A total of 12 trials evaluating behaviour therapy found positive effects on one or more indicators of QoL, for example, depression. The results of the review support recommendation of behaviour therapy in the care of patients with advanced cancer

Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial

Background: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. Methods: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. Findings: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90–1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. Interpretation: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. Funding: British Heart Foundation

Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club

Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment guidelines, with a critical assessment of the currently available efficacy data on all new chemical entities which were granted a marketing authorization. Osteoporosis is widely recognized as a major public health concern. The availability of new therapeutic agents makes clinical decision-making in osteoporosis more complex. Nation-specific guidelines are needed to take into consideration the specificities of each and every health care environment. The present manuscript is the result of a National Consensus, based on a systematic review and a critical appraisal of the currently available literature. It offers an evidence-based update of previous treatment guidelines, with the aim of providing clinicians with an unbiased assessment of osteoporosis treatment effect

A method to determine spatial access to specialized palliative care services using GIS

Background: Providing palliative care is a growing priority for health service administratorsworldwide as the populations of many nations continue to age rapidly. In many countries, palliativecare services are presently inadequate and this problem will be exacerbated in the coming years.The provision of palliative care, moreover, has been piecemeal in many jurisdictions and there islittle distinction made at present between levels of service provision. There is a pressing need todetermine which populations do not enjoy access to specialized palliative care services in particular.Methods: Catchments around existing specialized palliative care services in the Canadian provinceof British Columbia were calculated based on real road travel time. Census block face populationcounts were linked to postal codes associated with road segments in order to determine thepercentage of the total population more than one hour road travel time from specialized palliativecare.Results: Whilst 81% of the province\u27s population resides within one hour from at least onespecialized palliative care service, spatial access varies greatly by regional health authority. Based onthe definition of specialized palliative care adopted for the study, the Northern Health Authorityhas, for instance, just two such service locations, and well over half of its population do not havereasonable spatial access to such care.Conclusion: Strategic location analysis methods must be developed and used to accurately locatefuture palliative services in order to provide spatial access to the greatest number of people, andto ensure that limited health resources are allocated wisely. Improved spatial access has thepotential to reduce travel-times for patients, for palliative care workers making home visits, and fortravelling practitioners. These methods are particularly useful for health service planners – andprovide a means to rationalize their decision-making. Moreover, they are extendable to a numberof health service allocation problems

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

Prevalence of Epistasis in the Evolution of Influenza A Surface Proteins

The surface proteins of human influenza A viruses experience positive selection to escape both human immunity and, more recently, antiviral drug treatments. In bacteria and viruses, immune-escape and drug-resistant phenotypes often appear through a combination of several mutations that have epistatic effects on pathogen fitness. However, the extent and structure of epistasis in influenza viral proteins have not been systematically investigated. Here, we develop a novel statistical method to detect positive epistasis between pairs of sites in a protein, based on the observed temporal patterns of sequence evolution. The method rests on the simple idea that a substitution at one site should rapidly follow a substitution at another site if the sites are positively epistatic. We apply this method to the surface proteins hemagglutinin and neuraminidase of influenza A virus subtypes H3N2 and H1N1. Compared to a non-epistatic null distribution, we detect substantial amounts of epistasis and determine the identities of putatively epistatic pairs of sites. In particular, using sequence data alone, our method identifies epistatic interactions between specific sites in neuraminidase that have recently been demonstrated, in vitro, to confer resistance to the drug oseltamivir; these epistatic interactions are responsible for widespread drug resistance among H1N1 viruses circulating today. This experimental validation demonstrates the predictive power of our method to identify epistatic sites of importance for viral adaptation and public health. We conclude that epistasis plays a large role in shaping the molecular evolution of influenza viruses. In particular, sites with , which would normally not be identified as positively selected, can facilitate viral adaptation through epistatic interactions with their partner sites. The knowledge of specific interactions among sites in influenza proteins may help us to predict the course of antigenic evolution and, consequently, to select more appropriate vaccines and drugs