A proposed modification to the McDonald 2010 criteria for the diagnosis of primary progressive multiple sclerosis.

BACKGROUND: The diagnostic criteria for primary-progressive multiple sclerosis (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the McDonald criteria. The aim of this study was to examine the sensitivity of the diagnostic criteria for PPMS with particular reference to spinal cord criteria and examine the utility of CSFOBs in a cohort of PPMS patients. METHODS: All new PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details and paraclinical evaluations including MRI of the brain, spinal cord, CSF and visually evoked responses (VERs) were assessed. The proportion of patients who met the requirements for diagnosis of PPMS on the basis of Thompson's and the McDonald Criteria (2001, 2005, 2010) were determined. RESULTS: There were 88/95 PPMS patients who had at least two diagnostic investigations. The sensitivity of Thompson's and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the greatest number of patients demonstrating dissemination in space (DIS) on only two investigations. VERs did not aid diagnosis. Reducing requirements for the number of spinal cord lesions (symptomatic or not) to one increased diagnostic sensitivity to 84%. CONCLUSION: An alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for PPMS.

Public health skills for a lay workforce: findings on skills and attributes from a qualitative study of lay health worker roles.

OBJECTIVES: To present a typology of attributes associated with lay health worker (LHW) roles drawn from a qualitative study of lay roles in the delivery of public health programmes. STUDY DESIGN: Qualitative research study of case studies of public health projects. METHODS: Five case studies of public health projects were undertaken, reflecting diverse roles, public health issues and populations. Semi-structured interviews and focus groups were carried out with a sample of 136 stakeholders, including commissioners, practitioners, LHWs and service users. Thematic analysis was conducted within and across cases. RESULTS: Findings on the pre-eminence of social skills associated with LHW roles were consistent across all five projects. Being approachable, non-judgemental and responsive to community needs were critical attributes that enabled LHWs to undertake outreach and communicate successfully with programme recipients. Experiential knowledge and cultural understanding were also important qualities. A typology of attributes associated with LHW roles is presented. CONCLUSIONS: Social skills, the ability to connect with a community, and the ability to develop respectful relationships are fundamental qualities for LHW roles. Further research would be required to produce a comprehensive map of LHW skills; however, the paper questions assumptions that lay skills are necessarily of a lower order than the professional skill set.

Lay perspectives on lay health worker roles, boundaries and participation within three UK community-based health promotion projects.

This paper examines lay interpretations of lay health worker roles within three UK community-based health promotion projects. It argues that understanding lay health worker roles requires critical analysis of the complex interrelationships between professionals, lay workers and the communities receiving a programme. Findings are presented that are drawn from a qualitative study of lay engagement in public health programme delivery where a key objective was to examine the perspectives of community members with the experience of receiving services delivered by lay health workers. Interviews and focus groups were conducted with 46 programme recipients from three case study projects; a breastfeeding peer support service, a walking for health scheme and a neighbourhood health project. The results show how participants interpreted the function and responsibilities of lay health workers and how those roles provided personalized support and facilitated engagement in group activities. Further insights into community participation processes are provided revealing the potential for active engagement in both formal and informal roles. The paper concludes that social relationships are core to understanding lay health worker programmes and therefore analysis needs to take account of the capacity for community members to move within a spectrum of participation defined by increasing responsibility for others.

Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype.

BACKGROUND: The relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that north-south differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study. PATIENTS AND METHODS: Patients and matched control subjects were identified in counties Donegal, Wexford and South Dublin through multiple sources. Prevalence was determined. Blood samples were taken for serum 25(OH)D and serum intact parathyroid hormone measurement, and DNA was extracted. RESULTS: Prevalence in 2007 was significantly greater in Donegal (northwest) (290.3/105, 95% CI 262.3 to 321.7) compared with 2001 (184.6/105; 162 to 209.5). In Wexford (southeast), there was a non-significant increase in prevalence in 2007 compared with 2001. Prevalence was significantly higher in Donegal than in Wexford (144.8/105; 126.7 to 167.8, p<0.0001) and South Dublin (127.8/105; 111.3 to 148.2, p<0.0001). Overall, mean 25(OH)D levels were low and did not differ between patients (38.6 nmol/l) and controls (36.4 nmol/l) However, significantly more patients than controls had 25(OH)D levels <25 nmol/l (deficiency) (p=0.004). Levels of 25(OH)D (mean 50.74 nmol/l) were significantly higher in South Dublin (area with lowest prevalence) (p<0.0001) than in Donegal or Wexford. HLA DRB1*15 occurred most frequently in Donegal (greatest MS prevalence) and least frequently in South Dublin. CONCLUSION: Vitamin D deficiency is common in Ireland. Latitudinal variation in MS probably relates to an interaction between genetic factors and environment (25(OH)D levels), and MS risk may be modified by vitamin D in genetically susceptible individuals.

Multiple sclerosis, from referral to confirmed diagnosis: an audit of clinical practice.

BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) guidelines recommend a timeline of 6 weeks from referral to neurology consultation and then 6 weeks to a diagnosis of multiple sclerosis (MS). OBJECTIVES: We audited the clinical management of all new outpatient referrals diagnosed with MS between January 2007 and May 2010. METHODS: We analysed the timelines from referral to first clinic visit, to MRI studies and lumbar puncture (LP) (if performed) and the overall interval from first visit to the time the diagnosis was given to the patient. RESULTS: Of the 119 diagnoses of MS/Clinically Isolated Syndrome (CIS), 93 (78%) were seen within 6 weeks of referral. MRI was performed before first visit in 61% and within 6 weeks in a further 27%. A lumbar puncture (LP) was performed in 83% of all patients and was done within 6 weeks in 78%. In total, 63 (53%) patients received their final diagnosis within 6 weeks of their first clinic visit, with 57 (48%) patients having their diagnosis delayed. The main rate-limiting steps were the availability of imaging and LP, and administrative issues. CONCLUSIONS: We conclude that, even with careful scheduling, it is difficult for a specialist service to obtain MRI scans and LP results so as to fulfil NICE guidelines within the optimal six-week period. An improved service would require MRI scans to be arranged before the first clinic visit in all patients with suspected MS.

Preliminary evidence for correlation between PASAT performance and P3a and P3b amplitudes in progressive multiple sclerosis.

BACKGROUND: The no-go P3a event-related potential (ERP) is a measure of attentional engagement and the P3b is a measure of context updating. The aim of this study was to compare ERP topographies: (i) to Paced Auditory Serial Addition Test (PASAT) results, (ii) of visual and auditory P3a and P3b of patients with primary progressive multiple sclerosis (PPMS) versus patients with secondary-progressive multiple sclerosis (SPMS) and (iii) of both progressive subtypes to healthy controls. METHODS: Thirty subjects (10 PPMS, 10 SPMS and 10 age-matched controls) completed visual and auditory no-go P3a and P3b tasks whilst data were recorded from a 128-scalp channel electroencephalography (EEG) array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: For the patients with multiple sclerosis (MS), PASAT score correlated significantly with parietal regions in the auditory P3b, auditory P3a and visual P3b conditions, and with central regions in the visual P3a condition. Patients with PPMS had significantly lower amplitude than patients with SPMS in the auditory P3b condition over the parietal area. The control group had greater amplitude than the patients with MS in all the P3 tasks, with the exception of the auditory P3b. CONCLUSIONS: These data suggest that PASAT performance and P3 ERPs correlate for MS progressive subtypes and that PPMS and SPMS differ in electrophysiological responses during auditory P3b tasks.

Optimising and profiling pre-implementation contexts to create and implement a public health network intervention for tackling loneliness.

BACKGROUND: The implementation of complex interventions experiences challenges that affect the extent to which they become embedded and scaled-up. Implementation at scale in complex environments like community settings defies universal replication. Planning for implementation in such environments requires knowledge of organisational capacity and structure. Pre-implementation work is an important element of the early phase of preparing the setting for the introduction of an intervention, and the factors contributing towards the creation of an optimal pre-implementation community context are under-acknowledged. METHODS: To explore the factors contributing towards the creation of an optimal pre-implementation context, a quasi-ethnographic approach was taken. The implementation of a social network intervention designed to tackle loneliness in a community setting acts as the case in example. Observations (of meetings), interviews (with community partners) and documentary analysis (national and local policy documents and intervention resources) were conducted. Layder's adaptive theory approach was taken to data analysis, with the Consolidated Framework for Implementation Research (CFIR) and a typology of third-sector organisations used to interpret the findings. RESULTS: Community settings were found to sit along a continuum with three broad categories defined as Fully Professionalised Organisations; Aspirational Community, Voluntary and Social Enterprises; and Non-Professionalised Community-Based Groups. The nature of an optimal pre-implementation context varied across these settings. Using the CFIR, the results illustrate that some settings were more influenced by political landscape (Fully professional and Aspirational setting) and others more influenced by their founding values and ethos (Non-Professionalised Community-Based settings). Readiness was achieved at different speeds across the categories with those settings with more resource availability more able to achieve readiness (Fully Professional settings), and others requiring flexibility in the intervention to help overcome limited resource availability (Aspirational and Non-Professionalised Community-Based settings). CONCLUSIONS: The CFIR is useful in highlighting the multiple facets at play in creating the optimal pre-implementation context, and where flex is required to achieve this. The CFIR illuminates the similarities and differences between and across settings, highlighting the complexity of open system settings and the important need for pre-implementation work. TRIAL REGISTRATION: ISRCTN19193075.

The survival of Salmonella enterica serovar Typhimurium DT104 and total viable counts on beef surfaces at different relative humidities and temperatures.

AIMS: The aim of this study was to investigate changes in Salmonella and total viable count (TVC) survival on beef carcass surfaces stored for 72 h under different combinations of relative humidity (i.e. RH 75% or 96%) and temperature (5 degrees C or 10 degrees C). METHODS AND RESULTS: The influence of low water activity (a(w)) and temperature on the survival and growth of Salmonella enterica serovar Typhimurium DT104 and the aerobic mesophilic flora on meat pieces from different sites on beef carcasses was investigated, under controlled conditions (75% or 96% RH; 5 or 10 degrees C) in an environmental cabinet. Salmonella counts declined during storage at low a(w) (75% RH) conditions at 5 degrees C or 10 degrees C. Salmonella counts increased during storage at high a(w) (96% RH) at 10 degrees C only. At 5 degrees C, TVCs increased during storage at high a(w), but not at low a(w). TVCs increased on all samples from carcasses stored at high or low a(w) at 10 degrees C, except those samples taken from areas of surface fat. CONCLUSIONS: This suggests that substrate composition dictates growth rates under low a(w) conditions. The results are discussed in terms of the possible protective effects of substrate osmolyte accumulation in bacterial survival and/or growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The data obtained in this study provides useful insights on the influence of a(w) and temperature on pathogen survival on meat surfaces at chill temperature.

Changes in life expectancy 1900-1990.

Life expectancy at birth has risen in all industrialized countries during the last 100 years, but mortality improvements by gender and region often have proceeded at very different rates. Although some countries have experienced increases in overall mortality during recent decades, the levels of life expectancy gains in countries such as Japan have confounded demographic predictions and have led to renewed research and debate over future mortality decline and the limits to human life. This paper reviews levels of and changes in life expectancy at birth and at older ages in industrialized countries during the 20th century. Trends in mortality and morbidity at older ages are summarized in the context of the historic epidemiological disease transition from infectious to chronic. Cause-specific and active/inactive decompositions of life expectancy are examined, as are initial attempts to correlate life expectancy with physical attributes that may reflect differential nutritional status.

Demographic Imperative.

That we live in an aging world is now well recognized. The steady, sustained growth of elderly populations is posing a considerable challenge to policymakers and after the turn of the century the numbers and proportions of elderly will rise rapidly in most developed and many developing countries. The increased numbers of the oldest members of the elderly population will generate special concerns. The well-documented survival advantage of women over men may be tempered by the suggestion that men spend a greater portion of life in an active, nondisabled state than women. Cross-national demographic and epidemiologic data may be used for defining and sharpening national policies that address aging populations.

Urban and rural dimensions of global population aging: an overview.

In keeping with the worldwide pattern of increased urbanization, the elderly population has become more concentrated in urban areas during the past 50 years. In developed countries as a whole, an estimated 73 percent of people aged 65 or over lived in urban areas in 1990, a figure that is projected to reach 80 percent by the year 2015. In developing nations, which are still predominantly rural, just over one-third of people aged 65 or over lived in urban areas in 1990, projected to exceed one-half by 2015. This article provides an overview of global data on urban elders, examines extant data on gender balances and migration patterns, and considers the importance of subnational urban/rural differences and whether rural elderly are disadvantaged relative to their urban counterparts.

Change in PASAT performance correlates with change in P3 ERP amplitude over a 12-month period in multiple sclerosis patients.

OBJECTIVE: To examine the correlation between the change in PASAT and the change in P3 event-related potentials (ERPs) over a 12-month period in multiple sclerosis (MS) patients, and to compare the 12-month change in the P3 ERP between MS patients and controls. METHODS: Forty-four subjects (27 MS patients, 17 controls) completed visual and auditory two-stimulus oddball and three-stimulus oddball tasks at Month 0 and Month 12. Data were recorded from a 128-scalp channel electroencephalography array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Amplitude, topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: The change in visual and auditory P3a correlated significantly with the change in PASAT score (r=0.56, p<0.001 and r=0.48, p=0.003, respectively). Visual P3b and P3a showed greater decrease in 12 months in MS patients relative to controls. Visual P3b, auditory P3b and auditory P3a amplitudes had significantly decreased in MS patients after 12-month period. CONCLUSIONS: Change in visual and auditory P3a ERP amplitudes correlate with change in PASAT scores in MS patients. Visual modality is more sensitive to changes in P3 ERP amplitudes over 12-month period. SIGNIFICANCE: P3 ERPs may have utility in monitoring the change in cognitive functioning in MS.

Impaired information processing speed and attention allocation in multiple sclerosis patients versus controls: a high-density EEG study.

BACKGROUND: The no-go P3a is a variant of the P300 event-related potential (ERP) that indexes speed of information processing and attention allocation. The aim of this study was to compare ERP findings with results from the paced auditory serial addition test (PASAT) and to quantify latency, amplitude and topographical differences in P3a ERP components between multiple sclerosis (MS) patients and controls. PATIENTS AND METHODS: Seventy-four subjects (20 relapsing remitting (RRMS) patients, 20 secondary progressive (SPMS) patients and 34 controls) completed a three-stimulus oddball paradigm (target, standard, and non-target). Subjects participated in separate visual and auditory tasks while data were recorded from 134 EEG channels. Latency differences were tested using an ANCOVA. Topographical differences were tested using statistical parametric mapping. RESULTS: Visual P3a amplitude correlated with PASAT score in all MS patients over frontal and parietal areas. There were significant differences in latency, amplitude, and topography between MS patients and controls in the visual condition. RRMS and SPMS patients differed in visual P3a latency and amplitude at frontal and parietal scalp regions. In the auditory condition, there were latency differences between MS patients and controls only over the parietal region. CONCLUSION: The present results demonstrate that information processing speed and attention allocation are impaired in MS.

A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.

The influence of attachment to beef surfaces on the survival of cells of Salmonella enterica serovar Typhimurium DT104, at different a(w) values and at low storage temperatures.

This study investigated the influence of attachment to beef surfaces on the survival, injury and death of stationary phase cells of Salmonella enterica serovar Typhimurium DT104, compared to cells free in solution. The effects on cells are considered at different a(w) values and low temperatures in relation to osmotic and cold temperature shock effects. Attachment of cells to meat surfaces prevented cell injury and death from hyperosmosis and low temperatures, compared to meat solutions. Storage of cells for 72h resulted in higher levels of cell death on cells attached to meat surfaces. The improved survival of cells in solutions was considered to be related to adaptation to osmotic stress as a result of exposure to a previous hyperosmotic shock and the ability of the cells to produce cold shock proteins. Pathogen cell growth at low temperatures is discussed in relation to the presence of low levels of NaCl. Finally the data is discussed in relation to pathogen survival on beef carcass surfaces during refrigeration.

Prevalence and molecular characterization of Escherichia coli O157:H7 on Irish lamb carcasses, fleece and in faeces samples.

AIMS: To determine the prevalence, seasonal variation and virulence characteristics of Escherichia coli O157:H7 in lambs presented for slaughter in Ireland. METHODS AND RESULTS: Over a 13-month period, pre- and postchill carcass swabs, faeces and fleece samples from 1600 lambs were examined for the presence of E. coli O157:H7. Escherichia coli O157:H7 was isolated from 5.75% (23/400) of fleece samples, 1.5% (6/400) of pre- and 1% (4/400) of postchill carcass swabs but was not isolated in faeces (0/400). The present study detected no evidence of seasonal variation. Polymerase chain reaction analysis showed that both the vt1 and vt2 genes associated with clinical illness were carried by five of the E. coli O157:H7 isolates, while 24 of the remaining isolates carried the vt2 gene only. Phage typing detected four different subtypes: PT 32 (48.48%), PT 8 (12.12%), PT 31 (12.12%) and PT 21/28 (12.12%). CONCLUSIONS: Escherichia coli O157:H7 is present in lambs at slaughter in Irish abattoirs and the virulence profiles of these isolates reveals that they are potentially harmful to humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides crucial information indicating that sheep may be a significant contributing source to human E. coli O157:H7 infection.

Impact of a novel spray-chilling system on surface microflora, water activity and weight loss during beef carcass chilling.

Commercially slaughtered and dressed beef carcass sides (n=30) were followed through a standard commercial chill unit fitted with a new "Jasca" air humidification system adjusted to provide intermittent water spraying of carcass sides (spray cycle 2 min on, 1 min off) for 15 h. Immediately after dressing, and after 24h in the chill unit, the surface water activity, and the weight of each side was measured, and 5 cm2 samples were recovered from four locations, i.e. rump, flank, brisket and neck on the surface of each side. These samples, and similar samples from control sides (n=30) processed in a standard commercial chill unit, were subjected to microbiological examination by direct and resuscitation counts on plate count agar (PCA), MacConkey agar (MAC) and violet red bile glucose agar (VRBGA). No significant differences were observed between bacterial numbers on test and control samples on each of the above agars, at each sample point/occasion. Comparison of direct and resuscitation counts suggested the presence of substantial numbers of injured cells, at both stages (pre- and post-chill), on test and control sides. After 24 h in chill units, test sides exhibited an average weight loss of 1.36% (+/-0.36%), which is significantly less (P<0.001) than the average weight loss (1.55%+/-0.24%) from control sides. These results suggest that the Jasca spray-chilling system can limit carcass shrinkage (on average by 0.19%) without significantly increasing the surface populations of selected bacterial groups.