The role of specialist nurses in multiple sclerosis : a rapid and systematic review

Background Multiple sclerosis (MS) is a disease of the central nervous system. The cause is unknown. There are about 80–160 people with MS per 100,000 population, with twice as many women affected as men. The management of individuals with MS includes treatment of acute relapses and chronic symptoms. The care of MS patients is provided by various healthcare professionals, such as general practitioners (GPs), neurologists, physiotherapists, occupational therapists and nurses. Some MS patients have access to an MS specialist nurse, although this provision varies geographically. Objectives The aim of this report is to assess the effectiveness and relative cost-effectiveness of MS specialist nurses in improving care and outcomes for patients with MS. Methods A systematic review of the literature, involving a range of databases, was performed. Full details are described in the main report. Results Only one study was identified that tried to evaluate the benefit of MS specialist nurses. The study concluded that MS patients and their carers found the MS specialist nurse to be helpful, particularly in improving their knowledge of MS, ability to cope, mood and confidence about the future. GPs also reported finding the nurse to be helpful with their MS patients, and 40% of the GPs stated they would purchase the services of an MS specialist nurse if their practices became fundholding. However, there were considerable methodological weaknesses inherent in the study design, and it was unclear whether the results of the study could be extrapolated to other settings or to other MS patient groups. Ongoing research There are two ongoing research studies regarding MS specialist nurses. One of these studies involves the provision of MS nurses to several areas, but also has two control populations to allow evaluation of the health benefits of the nurses to MS patients and their carers. This study will help to fill the evidence gap. Costs The costs of providing MS specialist nurses consist of their yearly salary (usually NHS grade G), as well as additional costs for travelling, administration, computer and telephone use, a pension scheme, National Insurance and study leave. The MS Society of Great Britain and Northern Ireland allows a generous total yearly cost to the employer of £40,000. Conclusions The present evidence does not make it possible to comment with any certainty on the value of specialist nurses in MS. The best evidence available to the authors is specialist opinion from neurologists and nurses, and comments from patients with MS; this opinion supports the provision of MS specialist nurses. Recommendations for research Further research is needed before it will be feasible to make firm recommendations on the value of MS specialist nurses relative to other possible uses of funds

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments.

Immunotargeting of PLAP-expressing tumours was studied for two radioiodinated, highly specific anti-PLAP monoclonal antibodies, 7E8 and 17E3, differing 10-fold in affinity, as well as for 7E8 F(ab')2 fragments. An anti-CEA monoclonal antibody or anti-CD3 F(ab')2 fragments were used as controls. Specific and non-specific targeting was examined in nude mice simultaneously grafted with PLAP-positive tumours derived from MO4 1-4 cells, and CEA-positive tumours, derived from 5583-S cells. Results indicated that (1) MO4 1-4 tumours, with a stable expression of PLAP on the plasma membrane, represent a useful new in vivo model for immunodirected tumour targeting; (2) differences in antibody affinity for PLAP in vitro are not reflected in antibody avidity for tumour cells in vivo; and (3) excellent selective and specific localisation of the PLAP-positive tumours is achieved when 7E8 F(ab')2 fragments are used. The high tumour/blood ratios (10.7 +/- 3.9 at 46 h after injection) were due to a much faster blood clearance of 7E8 F(ab')2 fragments. At this time point, the mean tumour/non-tumour tissue ratio was as high as 34.5, and the mean specific localisation index was 29.0. As expected, the F(ab')2 fragments provided high tumour imaging efficiency on gamma camera recording. These data imply important potentials of the PLAP/anti-PLAP system for immunolocalisation and therapy in patients, but also emphasise that in vitro criteria alone are not reflected in in vivo tumour localisation capacities of antibodies

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data extraction and synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main outcomes and measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study registration: PROSPERO CRD42019119288This study was supported by the Gieskes-Strijbis Foundation, Alzheimer Netherlands, and the Dutch Young-Onset Dementia Knowledge Centre

Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI

Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process

Still too far to walk: Literature review of the determinants of delivery service use

BACKGROUND: Skilled attendance at childbirth is crucial for decreasing maternal and neonatal mortality, yet many women in low- and middle-income countries deliver outside of health facilities, without skilled help. The main conceptual framework in this field implicitly looks at home births with complications. We expand this to include "preventive" facility delivery for uncomplicated childbirth, and review the kinds of determinants studied in the literature, their hypothesized mechanisms of action and the typical findings, as well as methodological difficulties encountered. METHODS: We searched PubMed and Ovid databases for reviews and ascertained relevant articles from these and other sources. Twenty determinants identified were grouped under four themes: (1) sociocultural factors, (2) perceived benefit/need of skilled attendance, (3) economic accessibility and (4) physical accessibility. RESULTS: There is ample evidence that higher maternal age, education and household wealth and lower parity increase use, as does urban residence. Facility use in the previous delivery and antenatal care use are also highly predictive of health facility use for the index delivery, though this may be due to confounding by service availability and other factors. Obstetric complications also increase use but are rarely studied. Quality of care is judged to be essential in qualitative studies but is not easily measured in surveys, or without linking facility records with women. Distance to health facilities decreases use, but is also difficult to determine. Challenges in comparing results between studies include differences in methods, context-specificity and the substantial overlap between complex variables. CONCLUSION: Studies of the determinants of skilled attendance concentrate on sociocultural and economic accessibility variables and neglect variables of perceived benefit/need and physical accessibility. To draw valid conclusions, it is important to consider as many influential factors as possible in any analysis of delivery service use. The increasing availability of georeferenced data provides the opportunity to link health facility data with large-scale household data, enabling researchers to explore the influences of distance and service quality

The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P = .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally