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In low- and middle-income countries (LMICs) striving to achieve universal health coverage, the involvement of different stakeholders in formal or informal ways in health technology assessment (HTA) must be culturally and socially relevant and acceptable. Challenges may be different from those seen in high-income countries. In this article, we aimed to pilot a questionnaire for uncovering the context-related aspects of patient and citizen involvement (PCI) in LMICs, collecting experiences encountered with PCI, and identifying opportunities for patients and citizens toward contributing to local decision- and policy-making processes related to health technologies.
Through a collaborative, international multi-stakeholder initiative, a questionnaire was developed for describing each LMIC's healthcare system context and the emergence of opportunities for PCI relating to HTA. The questionnaire was piloted in the first set of countries (Brazil, Indonesia, Nigeria, and South Africa).
The questionnaire was successfully applied across four diverse LMICs, which are at different stages of using HTA to inform decision making. Only in Brazil, formal ways of PCI have been defined. In the other countries, there is informal influence that is contingent upon the engagement level of patient and citizen advocacy groups (PCAGs), usually strongest in areas such as HIV/AIDS, TB, oncology, or rare diseases.
The questionnaire can be used to analyze the options for patients and citizens to participate in HTA or healthcare decision making. It will be rolled out to more LMICs to describe the requirements and opportunities for PCI in the context of LMICs and to identify possible routes and methodologies for devising a more systematic and formalized PCI in LMICs.
To evaluate the efficacy and tolerability of once-daily quetiapine XR adjunctive to antidepressant therapy versus antidepressant alone in patients with MDD showing an inadequate response to antidepressant treatment (mainly SSRIs/SNRIs).
6-week, multicentre, double-blind, parallel-group study (D1448C00007). Patients were randomised to receive quetiapine XR 150mg/day (n=167), 300mg/day (n=163) or placebo (n=163) as add-on to maintained antidepressant treatment. Primary endpoint: baseline to Week 6 change in MADRS total score. Secondary variables included: baseline to Week 1 change in MADRS total score; baseline to Week 6 change in HAM-A total and psychic anxiety subscale scores. Safety assessments included AE reporting.
Mean change in MADRS total score (overall baseline mean, 28.4) from baseline to Week 6 was significant (p<0.01) for quetiapine XR 150mg/day (-15.26) and 300mg/day (-14.94) versus placebo (-12.21). Separation from placebo in MADRS total score was apparent from Week 1 for both quetiapine doses (p<0.001).
At Week 6, mean change from baseline in HAM-A total score (overall baseline mean, 20.8) was significant for quetiapine XR 150mg/day (-10.27, p<0.01) and 300mg/day (-9.70, p<0.05) versus placebo (-7.92). Mean change from baseline in HAM-A psychic anxiety subscale score (overall baseline mean, 12.83) was significant with quetiapine XR 150mg/day (-6.82, p<0.001) and 300mg/day (-6.47, p<0.01) versus placebo (-5.11).
Most common AEs (>10%) were dry mouth, somnolence, fatigue, sedation, constipation and dizziness with quetiapine XR.
In patients with MDD with an inadequate response to antidepressant treatment, adjunctive quetiapine XR 150mg/day and 300mg/day was well tolerated and effective at reducing depressive and anxiety symptoms.
Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.
We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14–91% in reduction of disease cases.
Although financing represents a critical component of health system strengthening and also a defining concern of efforts to move towards universal health coverage, many countries lack the tools and capacity to plan effectively for service scale-up. As part of a multi-country collaborative study (the Emerald project), we set out to develop, test and apply a fully integrated health systems resource planning and health impact tool for mental, neurological and substance use (MNS) disorders.
A new module of the existing UN strategic planning OneHealth Tool was developed, which identifies health system resources required to scale-up a range of specified interventions for MNS disorders and also projects expected health gains at the population level. We conducted local capacity-building in its use, as well as stakeholder consultations, then tested and calibrated all model parameters, and applied the tool to three priority mental and neurological disorders (psychosis, depression and epilepsy) in six low- and middle-income countries.
Resource needs for scaling-up mental health services to reach desired coverage goals are substantial compared with the current allocation of resources in the six represented countries but are not large in absolute terms. In four of the Emerald study countries (Ethiopia, India, Nepal and Uganda), the cost of delivering key interventions for psychosis, depression and epilepsy at existing treatment coverage is estimated at US$ 0.06–0.33 per capita of total population per year (in Nigeria and South Africa it is US$ 1.36–1.92). By comparison, the projected cost per capita at target levels of coverage approaches US$ 5 per capita in Nigeria and South Africa, and ranges from US$ 0.14–1.27 in the other four countries. Implementation of such a package of care at target levels of coverage is expected to yield between 291 and 947 healthy life years per one million populations, which represents a substantial health gain for the currently neglected and underserved sub-populations suffering from psychosis, depression and epilepsy.
This newly developed and validated module of OneHealth tool can be used, especially within the context of integrated health planning at the national level, to generate contextualised estimates of the resource needs, costs and health impacts of scaled-up mental health service delivery.
Angiogenesis is a closely controlled biological process that takes place during fetal development of blood vessels and wound healing, and includes the development of new blood vessels from preexisting blood vessels. Tumor angiogenesis is a means by which tumors obtain oxygen, nutrition and promote tumor growth. Angiogenesis-regulating proteins are therefore ideal biomarkers in the study of tumor pathophysiology. In our laboratory, a new in silico-designed analogue of 2-methoxyestradiol has been synthesized with angiogenic properties, namely 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16). The ex vivo influence of ESE-16 on angiogenesis and morphology in platelets of healthy participants was investigated. Scanning electron microscopy revealed no morphological changes in ESE-16-treated platelets. The possible antiangiogenic effect of ESE-16-exposed platelets was determined by means of flow cytometry measurement of angiogenic protein levels, which were significantly increased after platelets were added to tumorigenic breast epithelial cells. This indicates that binding of platelets to cancer cells causes differential release of platelet constituents. Vascular endothelial growth factor levels were decreased in platelets, whereas platelet-derived growth factor and matrix metallopeptidase-9 levels were not significantly affected in platelets. In light of the above-mentioned data, further investigation of ESE-16’s influence on morphology and angiogenic markers in platelets of cancer patients is warranted.
The well-known recurrent nova T Pyx has brightened by 7 magnitudes, starting on 2011 April 14, its first eruption since 1966. T Pyx is unique amongst recurrent novæ in being surrounded by a nebula formed of material ejected during previous eruptions. The latest eruption therefore offers the rare opportunity to observe a light echo sweeping through the existing shell, and a new one forming. The sudden exposure of the existing shell to high-energy light is expected to result in a change of the dust morphology as well as in the part destruction of molecules. We observe this process in the near- and mid-IR during several epochs using ESO's VLT instruments Sinfoni, Visir and Isaac. Unfortunately, in the data analysed so far we only have a tentative detection in Brα from the shell, so might in the end have to be content with upper limits for the emission from the various molecular bands and ionised lines.
We report an extremely rare case of congenital cholesteatoma affecting the occipital bone.
We present a case report, plus a review of the world literature on similar lesions.
This case report describes the presentation and treatment of a congenital cholesteatoma arising in an apparently unique location within the occipital bone, with no effect on middle-ear structure or function. The different imaging characteristics of this lesion are described and illustrated. The discussion centres on the differentiation of this lesion from intradiploic epidermoid cysts, more commonly described in the neurosurgical literature. The possible methods of pathogenesis are discussed, along with treatment suggestions.
Congenital cholesteatomas and intradiploic epidermoid cysts are indistinguishable both histologically and radiologically, and would appear to be the same disease.
The success of efforts to re-establish mammalian carnivores within their former range is dependent on three key factors: methodological considerations, the biological requirements of the target species, and the involvement of local human communities for whom large carnivores pose a threat. We consider the role of these factors in the first 13 years of an effort to re-establish wild lions in northern KwaZulu-Natal Province, South Africa. We employed soft-release methods to mitigate the characteristic problems associated with restoration of large carnivores. A pre-release captivity period facilitated acclimatization of reintroduced lions and promoted long-term bonding of unfamiliar individuals into cohesive groups. All individuals remained in the release area and established enduring, stable home ranges. Reintroduced lions successfully reproduced and raised 78% of their cubs to independence. Human activity was the cause of all post-release mortality. Despite rapid population growth and the re-establishment of the species at Phinda Private Game Reserve, the population is small and isolated with little prospect for re-colonizing additional areas where the species has been extirpated, or for connecting with other isolated lion populations in the region. Accordingly, although we essentially overcame the short-term technical and biological challenges facing lion reintroduction, the long-term value of the Phinda population for addressing the conservation issues facing the species remains equivocal.
In the absence of good quality evidence for the effectiveness of specific aspects or formats of Cognitive Behavioural Therapy (CBT) supervision, it is necessary to consider what is recommended as good quality CBT supervision. This review of the literature aims to provide an overview of the recommended practice of CBT supervision by considering general principles and goals of CBT supervision; the format of individual supervision sessions; the course and stages of CBT supervision; attending to supervisees' cognitions and affects; the importance of the supervisory relationship as well as the recording and rating of therapy sessions. This could provide a framework for setting standards to aspire to and stimulate further research in this field. Conforming to such practice would be an important step toward quality assurance in CBT supervision.
A triad of retro-ocular pain, discharging ear and abducens nerve palsy, as described by Gradenigo, has been recognized for 150 years. It has traditionally been treated with surgery, but recent advances in imaging, allied with improved antibiotic treatment, allow conservative management of these cases. We present two cases of Gradenigo’s syndrome: a 6-year-old child and a 70-year-old man, both without cholesteatoma, who were managed without mastoidectomy. They both had full recovery of abducens nerve function, although this took 6 and 12 weeks, respectively. In order to manage patients with Gradenigo’s syndrome safely, accurate diagnostic radiology is essential, and our findings are presented and discussed. With changing medical technology, a review of the diagnostic and treatment options for this rare but serious condition, is timely.
Phase formation was studied in the Fe–Ge and Cr–Ge thin-film systems by means of Rutherford backscattering spectrometry and x-ray diffraction. In the Fe–Ge system, FeGe was the first phase to form while in the Cr–Ge system, Cr11Ge8 was found to form first. The results are compared with the predictions of the effective heat of formation model. Heats of formation were calculated using the Miedema model. The effect of the transformation enthalpy term ΔHtr, used to convert a semiconducting element into a hypothetical metallic one in the Miedema model, is also discussed.
Severe oxidation inhibited epitaxy when buried Sb profiles in single crystal silicon were formed from evaporated layers irradiated in atmosphere with a pulsed Q-switched ruby laser. Oxygen concentrations as high as 5×1017atoms/cm2 (equivalent to 105nm SiO2) were measured. However, structures prepared without the Sb layer and irradiated under identical conditions, showed no oxidation. Oxidation of Sb as a source of the measured oxygen was ruled out, while the total heating time during laser irradiation is so short (nano- to milliseconds) that normal oxidation kinetics cannot account for the amount of SiO2 measured. Irradiations in vacuum and in a helium ambient showed that the oxygen responsible for these effects is supplied from the ambient in which irradiations are carried out. Also no oxidation was observed when structures, prepared on a substrate heated to 350°C, were irradiated in atmosphere. A model to account for these oxidation effects is proposed.
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