Clinical outcomes of treatment with idebenone in Leber's hereditary optic neuropathy in the Netherlands:A national cohort study

Purpose The purpose of the study was to present results from a national Dutch cohort of patients with Leber's Hereditary Optic Neuropathy (LHON) treated with idebenone. Methods The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment. Results Data from 72 patients were analysed. Treatment duration was 23.8 +/- 14.4 (mean +/- SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 +/- 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced. Conclusion Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent

Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients

The aim of the study was to investigate the safety of adenosine 5′-triphosphate (ATP) administration at home in pre-terminal cancer patients. Included were patients with cancer for whom medical treatment options were restricted to supportive care, who had a life expectancy of less than 6 months, a World Health Organization performance status 1 or 2, and suffered from at least one of the following complaints: fatigue, anorexia or weight loss >5% over the previous 6 months. Side effects were registered systematically on a standard form according to the National Cancer Institute (NCI) Common Toxicity Criteria. Fifty-one patients received a total of 266 intravenous ATP infusions. Of these, 11 infusions (4%) were given at the lowest dose of 20 μg kg−1 min−1, 85 infusions (32%) at 25–40 μg kg−1 min−1, and 170 (64%) at the highest dose of 45–50 μg kg−1 min−1 ATP. The majority of ATP infusions (63%) were without side effects. Dyspnea was the most common side effect (14% of infusions), followed by chest discomfort (12%) and the urge to take a deep breath (11%). No symptoms of cardiac ischemia occurred in any of the infusions. All side effects were transient and resolved within minutes after lowering the ATP infusion rate. Side effects were most frequent in the presence of cardiac disorders. We conclude that ATP at a maximum dose of 50 μg kg−1 min−1 can be safely administered in the home setting in patients with pre-terminal cancer

Periphyton communities as biological polishing agents in mine waste waters and the precipitation process in tailings : final report.

Work on this project was conducted under the auspices of the Canada Centre for Mineral and Energy Technology, Energy, Mines and Resources Canada. DSS file no.: 028SQ.23440-0-9182; DSS contract no.: 23440-0-9182/01SQ; CANMET project no.: 9182; CANMET scientific authority: Ron McCready.Ecological Engineering as a decommissioning technology for acid-generating waste material from base metal mine sites is being developed on a site in northern Ontario. A zinc/copper concentrator operated 65 km northeast of Ear Falls for 10 years, producing about 760,000 short tons of tailings, covering 20 ha, and containing 41 % pyrite and 4 % pyrrhotite. The tailings are situated above a lake which has acidified during the life of the mine. Since 1986 the site has been investigated intensively. This report represents the last detailed investigation of the hydrology and geochemistry, concentrating on the oxidation and iron precipitation rates which occur in the tailings mass. These rates define the rate at which the contaminants are released. The released contaminants entering the acidified lake are removed in this Ecological Engineered system mainly by different groups of attached algae. A literature review was carried out to provide a technical framework for biological removal processes taking place on the site. Water samples collected from piezometers in 1990 were used to confirm that several precipitation processes could take place in the tailings mass or in the surface water receiving AMD seepage. All piezometer samples show super-saturation with respect to several iron minerals, including ferric hydroxides, aoethite, hematite, letidocrocite, and maanetite, which may be precipitated. Super-saturation with respect to iarosite is shown only by samples from 2 piezometers and Mill Pond. Samples from piezometers M4 and M10 (and from Mill Pond and Boomerang Landing) show super-saturation with respect to several aluminum minerals, including alunite, boehmite, diawore, gibbsite, and several clay minerals. Samples from piezometers M7B, MI 0, M25, M30, M47, M55, Mill Pond, and Dave's Dam show super-saturation with respect to quartz; those from M7B, MI 0, and M47 also show super-saturation with respect to gypsum. Revised sulphide-oxidation rates for the South Bay tailings range from 0.0001 to 0.0427 mol.kg" .yi' (overall average 0.0033 mol.kg-'.yi'). Revised Fe-precipitation rates range from 0.000009 to 0.001 135 mol.kg-'.yr-' (overall average 0.00025 mol.kg-'.yr-'). The literature review on periphytic algae indicated that algal growth rate data in acidic metal rich waters are scarce. However, the tolerance mechanisms of periphytic algal groups which facilitate growth and metal removal from the water were evident. Extracellular carbon in the form of sheaths or jelly is produced in response to metal and acid stress by the algal population. Extracellular carbon production is not only related to metal and acid stress, but also to low nutrients (P and N) in the water or plants. It was concluded that periphytic algae, given their biological polishing characteristics, will indeed prove to be an important contaminant removal process within the Ecological Engineering technology. Research is required to define the conditions which facilitate growth of periphytic algae, and which of the contaminant removal processes (biosieving, uptake, ad/absorption) is the main contaminant removal process. With this information, predictions on the contaminant removal capacity of the system can be made. With the contaminant release rates determined here, the overall effectiveness of biological polishing as a process can be determined

Incorporating a gender perspective into the development of clinical guidelines: a training course for guideline developers

<p>Abstract</p> <p>Background</p> <p>Dutch guideline-developing organizations do not focus systematically on differences between men and women when developing guidelines, even though there is increasing evidence that being male or female may have an effect on health and health outcomes. In collaboration with two prominent Dutch guideline-developing organizations, we designed a training course to encourage systematic attention to sex differences in guideline development procedures.</p> <p>Methods</p> <p>The course is targeted towards guideline developers. Its aims are to improve awareness concerning the relevance of considering sex differences in the guideline development process, as well as the competence and skills necessary for putting this into practice. The design and teaching methods of the course are based on adult learning styles and principles of changing provider behaviour. It was adjusted to the working methods of guideline organizations. The course was taught to, and evaluated by, a group of staff members from two guideline organizations in the Netherlands.</p> <p>Results</p> <p>The course consists of five modules, each of which corresponds to a key step in the guideline development process. The participants rated the training course positively on content, programme, and trainers. Their written comments suggest that the course met its objectives.</p> <p>Conclusion</p> <p>The training course is the first to address sex differences in guideline development. Results from the pilot test suggest that the course achieved its objectives. Because its modules and teaching methods of the course are widely transferable, the course could be useful for many organizations that are involved in developing guidelines. Follow-up studies are needed to assess the long-term effect of the course on the actions of guideline developers and its utility in other settings.</p

Can-Pain-a digital intervention to optimise cancer pain control in the community : development and feasibility testing

Purpose: To develop a novel digital intervention to optimise cancer pain control in the community. This paper describes intervention development, content/rationale and initial feasibility testing. Methods: Determinants of suboptimal cancer pain management were characterised through two systematic reviews; patient, caregiver and healthcare professional (HCP) interviews (n = 39); and two HCP focus groups (n = 12). Intervention mapping was used to translate results into theory-based content, creating the app “Can-Pain”. Patients with/without a linked caregiver, their general practitioners and community palliative care nurses were recruited to feasibility test Can-Pain over 4 weeks. Results: Patients on strong opioids described challenges balancing pain levels with opioid intake, side effects and activities and communicating about pain management problems with HCPs. Can-Pain addresses these challenges through educational resources, contemporaneous short-acting opioid tracking and weekly patient-reported outcome monitoring. Novel aspects of Can-Pain include the use of contemporaneous breakthrough analgesic reports as a surrogate measure of pain control and measuring the level at which pain becomes bothersome to the individual. Patients were unwell due to advanced cancer, making recruitment to feasibility testing difficult. Two patients and one caregiver used Can-Pain for 4 weeks, sharing weekly reports with four HCPs. Can-Pain highlighted unrecognised problems, promoted shared understanding about symptoms between patients and HCPs and supported shared decision-making. Conclusions: Preliminary testing suggests that Can-Pain is feasible and could promote patient-centred pain management. We will conduct further small-scale evaluations to inform a future randomised, stepped-wedge trial

A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

<p>Abstract</p> <p>Background</p> <p>Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted.</p> <p>Methods/design</p> <p>A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention.</p> <p>Discussion</p> <p>Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain will be implemented more widely.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01313234">NCT01313234</a></p

Hydro-biogeochemical coupling beneath a large polythermal Arctic glacier: Implications for subice sheet biogeochemistry

This article was published in the serial, Journal of Geophysical Research: Earth Surface [Wiley © American Geophysical Union]. It is also available at: http://dx.doi.org/10.1029/2009JF001602We analyze the interannual chemical and isotopic composition of runoff from a large, high Arctic valley glacier over a 5 year period, during which drainage evolved from a long-residence-time drainage system feeding an artesian subglacial upwelling (SGU) at the glacier terminus to a shorter-residence-time drainage system feeding an ice-marginal channel (IMC). Increased icemelt inputs to the SGU are thought to have triggered this evolution. This sequence of events provides a unique opportunity to identify coupling between subglacial hydrology and biogeochemical processes within drainage systems of differing residence time. The biogeochemistry of the SGU is consistent with prolonged contact between meltwaters and subglacial sediments, in which silicate dissolution is enhanced, anoxic processes (e.g., sulphate reduction) prevail, and microbially generated CO2 and sulphide oxidation drive mineral dissolution. Solute in the IMC was mainly derived from moraine pore waters which are added to the channel via extraglacial streams. These pore waters acquire solute predominantly via sulphide oxidation coupled to carbonate/silicate dissolution. We present the first evidence that microbially mediated processes may contribute a substantial proportion (80% in this case) of the total glacial solute flux, which includes coupling between microbial CO2-generation and silicate/carbonate dissolution. The latter suggests the presence of biofilms in subglacial/ice-marginal sediments, where local perturbation of the geochemical environment by release of protons, organic acids, and ligands stimulates mineral dissolution. These data enable inferences to be made regarding biogeochemical processes in longer-residence-time glacial systems, with implications for the future exploration of Antarctic subglacial lakes and other wet-based ice sheet environments

Self-management support intervention to control cancer pain in the outpatient setting: a randomized controlled trial study protocol

Background: Pain is a prevalent and distressing symptom in patients with cancer, having an enormous impact on functioning and quality of life. Fragmentation of care, inadequate pain communication, and reluctance towards pain medication contribute to difficulties in optimizing outcomes. Integration of patient self-management and professional care by means of healthcare technology provides new opportunities in the outpatient setting. Methods/Design: This study protocol outlines a two-armed multicenter randomized controlled trial that compares a technology based multicomponent self-management support intervention with care as usual and includes an effect, economic and process evaluation. Patients will be recruited consecutively via the outpatient oncology clinics and inpatient oncology wards of one academic hospital and one regional hospital in the south of the Netherlands. Irrespective of the stage of disease, patients are eligible when they are diagnosed with cancer and have uncontrolled moderate to severe cancer (treatment) related pain defined as NRS ≥ 4 for more than two weeks. Randomization (1:1) will assign patients to either the intervention or control group; patients in the intervention group receive self-management support and patients in the control group receive care as usual. The intervention will be delivered by registered nurses specialized in pain and palliative care. Important components include monitoring of pain, adverse effects and medication as well as graphical feedback, education, and nurse support. Effect measurements for both groups will be carried out with questionnaires at baseline (T0), after 4 weeks (T1) and after 12 weeks (T2). Pain intensity and quality of life are the primary outcomes. Secondary outcomes include self-efficacy, knowledge, anxiety, depression and pain medication use. The final questionnaire contains also questions for the economic evaluation that includes both cost-effectiveness and cost-utility analysis. Data for the process evaluation will be gathered continuously over the study period and focus on recruitment, reach, dose delivered and dose received. Discussion: The proposed study will provide insight into the effectiveness of the self-management support intervention delivered by nurses to outpatients with uncontrolled cancer pain. Study findings will be used to empower patients and health professionals to improve cancer pain control. Trial registration: NCT02333968 December 29, 201

Trends in publications regarding evidence-practice gaps: A literature review

<p>Abstract</p> <p>Background</p> <p>Well-designed trials of strategies to improve adherence to clinical practice guidelines are needed to close persistent evidence-practice gaps. We studied how the number of these trials is changing with time, and to what extent physicians are participating in such trials.</p> <p>Methods</p> <p>This is a literature-based study of trends in evidence-practice gap publications over 10 years and participation of clinicians in intervention trials to narrow evidence-practice gaps. We chose nine evidence-based guidelines and identified relevant publications in the PubMed database from January 1998 to December 2007. We coded these publications by study type (intervention versus non-intervention studies). We further subdivided intervention studies into those for clinicians and those for patients. Data were analyzed to determine if observed trends were statistically significant.</p> <p>Results</p> <p>We identified 1,151 publications that discussed evidence-practice gaps in nine topic areas. There were 169 intervention studies that were designed to improve adherence to well-established clinical guidelines, averaging 1.9 studies per year per topic area. Twenty-eight publications (34%; 95% CI: 24% - 45%) reported interventions intended for clinicians or health systems that met Effective Practice and Organization of Care (EPOC) criteria for adequate design. The median consent rate of physicians asked to participate in these well-designed studies was 60% (95% CI, 25% to 69%).</p> <p>Conclusions</p> <p>We evaluated research publications for nine evidence-practice gaps, and identified small numbers of well-designed intervention trials and low rates of physician participation in these trials.</p