Measuring coping in multiple sclerosis: The Coping Index-MS.

BACKGROUND: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores. OBJECTIVE: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement. METHODS: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations. RESULTS: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline. CONCLUSION: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.

BACKGROUND: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb weakness, dysarthria, emotional lability, and respiratory failure. Since normal salivary production is 0.5 L to 1.5 L daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to people with MND. This is an update of a review first published in 2011. OBJECTIVES: To assess the effects of treatments for sialorrhea in MND, including medications, radiotherapy and surgery. SEARCH METHODS: On 27 August 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov and the WHO ICTRP. We checked the bibliographies of the identified randomized trials and contacted trial authors as needed. We contacted known experts in the field to identify further published and unpublished papers. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs, including cross-over trials, on any intervention for sialorrhea and related symptoms, compared with each other, placebo or no intervention, in people with ALS/MND. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified four RCTs involving 110 participants with MND who were described as having intractable sialorrhea or bulbar dysfunction. A well-designed study of botulinum toxin B compared to placebo injected into the parotid and submandibular glands of 20 participants showed that botulinum toxin B may produce participant-reported improvement in sialorrhea, but the confidence interval (CI) was also consistent with no effect. Six of nine participants in the botulinum group and two of nine participants in the placebo group reported improvement (risk ratio (RR) 3.00, 95% CI 0.81 to 11.08; 1 RCT; 18 participants; low-certainty evidence). An objective measure indicated that botulinum toxin B probably reduced saliva production (in mL/5 min) at eight weeks compared to placebo (MD -0.50, 95% CI -1.07 to 0.07; 18 participants, moderate-certainty evidence). Botulinum toxin B may have little to no effect on quality of life, measured on the Schedule for Evaluation of Individual Quality of Life direct weighting scale (SEIQoL-DW; 0-100, higher values indicate better quality of life) (MD -2.50, 95% CI -17.34 to 12.34; 1 RCT; 17 participants; low-certainty evidence). The rate of adverse events may be similar with botulinum toxin B and placebo (20 participants; low-certainty evidence). Trialists did not consider any serious events to be related to treatment. A randomized pilot study of botulinum toxin A or radiotherapy in 20 participants, which was at high risk of bias, provided very low-certainty evidence on the primary outcome of the Drool Rating Scale (DRS; range 8 to 39 points, higher scores indicate worse drooling) at 12 weeks (effect size -4.8, 95% CI -10.59 to 0.92; P = 0.09; 1 RCT; 16 participants). Quality of life was not measured. Evidence for adverse events, measured immediately after treatment (RR 7.00, 95% CI 1.04 to 46.95; 20 participants), and after four weeks (when two people in each group had viscous saliva) was also very uncertain. A phase 2, randomized, placebo-controlled cross-over study of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate (DMQ) found that DMQ may produce a participant-reported improvement in sialorrhea, indicated by a slight improvement (decrease) in mean scores for the primary outcome, the Center for Neurologic Study Bulbar Function Scale (CNS-BFS). Mean total CNS-BFS (range 21 (no symptoms) to 112 (maximum symptoms)) was 53.45 (standard error (SE) 1.07) for the DMQ treatment period and 59.31 (SE 1.10) for the placebo period (mean difference) MD -5.85, 95% CI -8.77 to -2.93) with a slight decrease in the CNS-BFS sialorrhea subscale score (range 7 (no symptoms) to 35 (maximum symptoms)) compared to placebo (MD -1.52, 95% CI -2.52 to -0.52) (1 RCT; 60 participants; moderate-certainty evidence). The trial did not report an objective measure of saliva production or measure quality of life. The study was at an unclear risk of bias. Adverse events were similar to other trials of DMQ, and may occur at a similar rate as placebo (moderate-certainty evidence, 60 participants), with the most common side effects being constipation, diarrhea, nausea, and dizziness. Nausea and diarrhea on DMQ treatment resulted in one withdrawal. A randomized, double-blind, placebo-controlled cross-over study of scopolamine (hyoscine), administered using a skin patch, involved 10 randomized participants, of whom eight provided efficacy data. The participants were unrepresentative of clinic cohorts under routine clinical care as they had feeding tubes and tracheostomy ventilation, and the study was at high risk of bias. The trial provided very low-certainty evidence on sialorrhea in the short term (7 days' treatment, measured on the Amyotrophic Lateral Scelerosis Functional Rating Scale-Revised (ALSFRS-R) saliva item (P = 0.572)), and the amount of saliva production in the short term, as indicated by the weight of a cotton roll (P = 0.674), or daily oral suction volume (P = 0.69). Quality of life was not measured. Adverse events evidence was also very uncertain. One person treated with scopolamine had a dry mouth and one died of aspiration pneumonia considered unrelated to treatment. AUTHORS' CONCLUSIONS: There is some low-certainty or moderate-certainty evidence for the use of botulinum toxin B injections to salivary glands and moderate-certainty evidence for the use of oral dextromethorphan with quinidine (DMQ) for the treatment of sialorrhea in MND. Evidence on radiotherapy versus botulinum toxin A injections, and scopolamine patches is too uncertain for any conclusions to be drawn. Further research is required on treatments for sialorrhea. Data are needed on the problem of sialorrhea in MND and its measurement, both by participant self-report measures and objective tests. These will allow the development of better RCTs.

The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications.

BACKGROUND: Longitudinal studies among people with Multiple Sclerosis (pwMS) have shown that self-efficacy is linked to physical, cognitive and psychological functioning. OBJECTIVES: To determine the distribution of self-efficacy in a large sample of pwMS, examining whether there are distinct groups which show different self-efficacy trajectories over time, and the health status characteristics of any groups identified. METHODS: Participants completed serial questionnaire packs, including Unidimensional Self-efficacy-MS (USE-MS) scale, for the Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study over an average 46-month period. The resulting longitudinal data were analysed by a group-based trajectory model. RESULTS: 5887 pwMS were studied: mean age 50.2 years (SD 12.0); 73.6% female; Relapsing Remitting MS (61.8%), Secondary Progressive (22.9%), Primary Progressive (11.1%), Rapidly Evolving Relapsing Remitting MS (4.2%). Four distinct self-efficacy trajectories emerged, with declining, slightly declining, stable or improving self-efficacy, each showing different patterns of health status indicators such as EQ-5D-5L, disability and depression. USE-MS ≤ 18 at baseline detected all participants in the two declining groups. CONCLUSION: Future trials on interventions for self-efficacy should assume a priori that those with low levels of self-efficacy (USE-MS ≤ 18 at baseline) are likely to be on a declining trajectory and may need different interventions from those with stable self-efficacy.

The Association Between Benign Fasciculations and Health Anxiety: A Report of Two Cases and a Systematic Review of the Literature.

BACKGROUND: Benign fasciculation syndrome (BFS) is characterized by persistent spontaneous contractions of muscle fibers in the absence of a pathological cause. Patients with BFS often have concerns around having motor neuron disease, in some cases fulfilling the criteria for health anxiety disorder. Research on how BFS and health anxiety relate to one another and how they should be optimally managed together is sparse. OBJECTIVE: We report two cases of BFS associated with health anxiety. We also review the literature on the association between BFS and health anxiety. METHODS: We systematically reviewed the literature using MEDLINE, Embase, PsycINFO, and OpenGrey for studies investigating benign fasciculations and anxiety up to August 2018. RESULTS: Both cases were successfully treated for health anxiety disorder with cognitive-behavioral therapy (CBT) and antidepressant medication. We identified eight studies that met the inclusion criteria, describing a total of 384 patients. Most studies were of moderate quality. Patients with BFS tended to be male and in their 30s or 40s. There was an overrepresentation of clinicians. Anxiety symptoms were common and frequently coexisted alongside fasciculations. Health anxiety was overwhelmingly focused around motor neuron disease. CONCLUSION: A proportion of individuals with BFS experience anxiety around having motor neuron disease-to the point of developing health anxiety disorder. A bidirectional relationship may exist between BFS and health anxiety disorder. Clinicians should be alert to the possibility of health anxiety disorder in patients with BFS and have a low threshold to refer for psychiatric assessment. There is support for the role of psychological therapy, especially CBT, as well as pharmacotherapy, in the form of antidepressant medication. In severe or treatment-refractive cases, combined treatment may be indicated.

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116.

Objective: To model the effects of demographic change under various scenarios of possible future treatment developments in ALS. Methods: Patients diagnosed with ALS at the King's College Hospital Motor Nerve Clinic between 2004 and 2017, and living within the London boroughs of Lambeth, Southwark, and Lewisham (LSL), were included as incident cases. We also ascertained incident cases from the Canterbury region over the same period. Future incidence of ALS was estimated by applying the calculated age- and sex-specific incidence rates to the UK population projections from 2020 to 2116. The number of prevalent cases for each future year was estimated based on an established method. Assuming constant incidence, we modelled four possible future prevalence scenarios by altering the median disease duration for varying subsets of the population, to represent the impact of new treatments. Results: The total number of people newly diagnosed with ALS per year in the UK is projected to rise from a baseline of 1415 UK cases in 2010 to 1701 in 2020 and 2635 in 2116. Overall prevalence of ALS was predicted to increase from 8.58 per 100,000 persons in 2020 to 9.67 per 100,000 persons in 2116. Halting disease progression in patients with C9orf72 mutations would yield the greatest impact of the modelled treatment scenarios, increasing prevalence in the year 2066 from a baseline of 9.50 per 100,000 persons to 15.68 per 100,000 persons. Conclusions: Future developments in treatment would combine with the effects of demographic change to result in more people living longer with ALS.

Relative preservation of triceps over biceps strength in upper limb-onset ALS: the 'split elbow'.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system. The split hand sign in ALS refers to observed preferential weakness of the lateral hand muscles, which is unexplained. One possibility is larger cortical representation of the lateral hand compared with the medial. Biceps strength is usually preserved relative to triceps in neurological conditions, but biceps has a larger cortical representation and might be expected to show preferential weakness in ALS. METHODS: Using the South-East England Register for Amyotrophic Lateral Sclerosis, we performed a retrospective longitudinal cohort study and extracted the modified Medical Research Council (MRC) muscle strength score for biceps and triceps in patients with a diagnosis of upper limb-onset ALS in the 19-year period 1996-2015. A Wilcoxon signed-rank test was used to assess the relative strength of the muscles within the total sum of the upper limbs involved in the study. RESULTS: There were 659 people with upper limb onset of weakness. In 215 there were insufficient data to perform the analysis, and a further 33 were excluded for other reasons, leaving 411 for analysis. Biceps was stronger than triceps in 87 limbs, and triceps was stronger than biceps in 258 limbs, with no difference seen in the remaining 477. Triceps strength scores (mean rank=186.1) were higher than ipsilateral biceps strength scores (mean rank=134.2), Z=-10.1, p<0.001 (two-tailed). CONCLUSION: Triceps strength is relatively preserved compared with biceps in ALS. This is consistent with a broadly corticofugal hypothesis of selective vulnerability, in which susceptibility might be associated with larger cortical representation.

A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis.

Failure to clear oral secretions can be debilitating for patients with amyotrophic lateral sclerosis (ALS), but the treatment of this symptom is poorly defined and there is no consensus on best practice. The objective of this study was to identify the treatments that are commonly prescribed, and to describe how experienced clinicians manage a patient with treatment resistant symptoms. Twenty-three clinicians were approached, of which 19 from 16 centres across the UK provided case report forms for a total of 119 ALS patients identified as having problematic oral secretions. The use of five anticholinergics, salivary gland botulinum toxin injections, conservative management approaches and carbocisteine were reported. Of the 72 patients who were evaluated following the initiation of a first anticholinergic, 61% had symptomatic improvement. Only 19% of patients achieved symptomatic improvement with the use of an alternative anticholinergic when an initial anticholinergic achieved no symptomatic improvement. Problems with thick and thin secretions often coexisted, with 37% of patients receiving treatment for both types of problem. In conclusion, a variety of treatment options are employed by expert clinicians for problematic oral secretions in ALS patients. The variation in management highlights the need for further prospective research in this area.

Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis.

Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease.

Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis.

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

BACKGROUND: Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. METHODS: We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. FINDINGS: We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5). INTERPRETATION: A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. FUNDING: UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).

The evaluation of pain in amyotrophic lateral sclerosis: a case controlled observational study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive paralysis. ALS is complicated by a number of non-motor symptoms including pain. Pain in ALS has been poorly studied and poorly managed. This study aimed to collate information regarding pain in ALS using standardized pain questionnaires. Forty-two patients with ALS participated in the study. Control subjects included 41 age-matched healthy volunteers and 42 age-matched patients with neurological conditions other than ALS. Data on pain were collected using the The Brief Pain Inventory and The painDetect Questionnaire. Eighty-five percent of subjects with ALS reported pain versus 50% of neurology clinic controls and 35% of healthy controls (p < 0.01). Pain in ALS included cramping, aching, tiring, sharp and tender, and was non-neuropathic. Pain impacted significantly on mood, general activity, relationships and general enjoyment of life. Fifty-four percent of people with painful ALS used regular analgesia and 29% regular opioids. Other non-motor symptoms suffered included tiredness, constipation, urinary problems, itching and drowsiness. In conclusion, these data support the fact that pain is a significant symptom in ALS which impacts on quality of life. These data can be used to educate clinicians and patients to promote better multidisciplinary management of ALS symptoms and a better quality of life.

Evidence of an environmental effect on survival in ALS.

Amyotrophic lateral sclerosis (ALS, motor neuron disease) is a neurodegenerative disorder of motor neurons leading to paralysis and eventual death by respiratory failure. Median survival is 2-3 years. Susceptibility genes, environmental triggers and disease related prognostic factors have been established, but environmental effects on survival are yet to be investigated. We analysed survival in the South-East England ALS register (SEALS register). Kaplan-Meier and Cox regression analyses were used to investigate survival in London, coastal and rural areas according to postcode at diagnosis. Results showed that there were 933 cases of ALS identified in the catchment area during the study period (1994-January 2012). Cox regression demonstrated a highly significant model for survival with significant protective variables: coastal residency, riluzole use and younger age at onset. Significantly worse survival was associated with London residency, older age as well as definite and probable El Escorial classifications. In conclusion, these findings suggest the possibility of an environmental effect on survival in ALS.

Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis.

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Management of sialorrhoea in motor neuron disease: a survey of current UK practice.

Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres. Sixteen centres were specialist MND Care Centres. Clinicians estimated seeing a total of 1391 newly diagnosed patients with MND in 2011. One hundred and ninety-three patients were described. Forty-two percent of patients reviewed in clinicians' last clinic had sialorrhoea and 46% of those with sialorrhoea had uncontrolled symptoms. Clinicians' preferred drugs were hyoscine patches, amitriptyline, carbocisteine and botulinum toxin. Botulinum toxin was used in 14 centres. Risk of dysphagia and staff skills were identified as the main barriers to botulinum toxin use. This survey suggests that there may be as many as 1700 patients with MND in the UK who have symptoms of sialorrhoea and that symptoms may be poorly controlled in nearly half. Treatment strategies varied, reflecting the lack of evidence based guidelines. The use of specialist treatments was influenced by local infrastructure. This study highlights the need for further work to develop evidence based guidance.

Eating-derived pleasure in amyotrophic lateral sclerosis as a predictor of non-oral feeding.

Our objective was to examine the pleasure derived from eating in patients with advanced ALS and how this affects advice to have a gastrostomy. Patients with advanced ALS completed a visual analogue scale indicating the pleasure they derived from eating. Data were also collected on the severity of swallow using the Hillel scale, the independent feeding status, and on whether gastrostomy was accepted or not. The findings from 38 consecutive patients indicate that pleasure derived from eating is a powerful indicator of a person's acceptance of gastrostomy. In conclusion, the study showed that a simple analogue scale is quick and practical in a clinical setting even in severely compromised people with ALS and that the eating pleasure score was a strong predictor of the final decision to accept gastrostomy placement (p = 12.2 = 10(-4)).

No evidence for a large difference in ALS frequency in populations of African and European origin: a population based study in inner city London.

Abstract Previous studies have suggested a lower incidence of ALS in people of African origin. We used a population based register in an urban setting from inner city London postcodes where there is a large population of people of African ancestry to compare the frequency of ALS in people of European and African origin. Population statistics stratified by age, gender and ethnicity were obtained from the 2001 census. Incidence and prevalence were calculated in each ethnic group. Results showed that in a population of 683,194, of which 22% were of African ancestry, 88 individuals with ALS were identified over a seven-year period, including 14 people with African ancestry. The adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3) and in those of European ancestry 1.97 per 100,000 person-years (95% CI 1.55-2.48). In conclusion, in this small population based study we could not detect a difference in rates of ALS between people of African ancestry and those of European ancestry.

Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.

BACKGROUND: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a progressive, neurodegenerative condition which may cause dysphagia, as well as limb weakness, dysarthria, emotional lability and respiratory failure. Since normal salivary production is 0.5 to 1.5 litres daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to patients. OBJECTIVES: To systematically review evidence on treatment of sialorrhea in MND, including medications, radiotherapy and surgery. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Specialized Register (1 October 2010), the Cochrane Central Register of Controlled Trials )(CENTRAL) (The Cochrane Library issue 3, 2010), MEDLINE (January 1966 to September 2010), EMBASE (January 1980 to September 2010), AMED (1985 to September 2010) and CINAHL Plus (January 1937 September 2010). All bibliographies of the identified randomized trials were reviewed and authors contacted as needed. Known experts in the field were contacted to identify further published and unpublished papers. SELECTION CRITERIA: We included randomized and quasi-randomised controlled studies on any intervention for sialorrhea and related symptoms, in people with MND. DATA COLLECTION AND ANALYSIS: Review authors summarised data independently in a customised data collection form and confirmed data presented in Cochrane Review Manager software. MAIN RESULTS: Only one randomized controlled trial was identified. This was a well designed study of botulinum toxin B injected into parotid and submandibular glands of 20 patients, which showed positive results for four weeks (Jackson 2009). There was low risk of bias in the study and no significant adverse events reported. AUTHORS' CONCLUSIONS: There is some evidence for use of botulinum toxin injections to salivary glands for the treatment of sialorrhea in MND. Further research is required on this important symptom. Data are needed on the problem of sialorrhea in MND and its measurement, both by patient self report measures and objective tests. These will allow the development of better randomized controlled trials.

A new approach to patient-centered care.

An opportunity existed at our rehabilitation hospital, in preparation for Medicare's Prospective Payment System (PPS) in acute medical rehabilitation, to develop an integrated inpatient care model using all available resources. The results have been an improved practice of all staff, increased efficiency and productivity, and increased staff and patient satisfaction. This article discusses the drivers for changing the team model within a large rehabilitation hospital. It includes an overview of the process of data gathering prior to changing the team model, how the new team model functions, and follow-up data collection 9 months after to provide evidence on what changes worked and what areas required further change to meet the objectives.

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats.

RATIONALE: Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation. OBJECTIVES: To investigate the CNS role of NmU by mapping NMU1R and NMU2R mRNA and measuring the behavioural, endocrine, neurochemical and c-fos response to intracerebroventricular (i.c.v.) NmU. METHODS: Binding affinity and functional potency of rat NmU was determined at human NMU1R and NMU2R. Expression of NMU1R and NMU2R mRNA in rat and human tissue was determined using semi-quantitative reverse-transcription polymerase chain reaction. In in-vivo studies, NmU was administered i.c.v. to male Sprague-Dawley rats, and changes in grooming, motor activity and pre-pulse inhibition (PPI) were assessed. In further studies, plasma endocrine hormones, [DOPAC + HVA]/[dopamine] and [5-HIAA]/[5-HT] ratios and levels of Fos-like immunoreactivity (FLI) were measured 20 min post-NmU (i.c.v.). RESULTS: NmU bound to NMU1R ( K(I), 0.11+/-0.02 nM) and NMU2R ( K(I), 0.21+/-0.05 nM) with equal affinity and was equally active at NMU1R (EC(50), 1.25+/-0.05 nM) and NMU2R (EC(50), 1.10+/-0.20 nM) in a functional assay. NMU2R mRNA expression was found at the highest levels in the CNS regions of both rat and human tissues. NMU1R mRNA expression was restricted to the periphery of both species with the exception of the rat amygdala. NmU caused a marked increase in grooming and motor activity but did not affect PPI. Further, NmU decreased plasma prolactin but did not affect levels of corticosterone, luteinising hormone or thyroid stimulating hormone. NmU elevated levels of 5-HT in the frontal cortex and hypothalamus, with decreased levels of its metabolites in the hippocampus and hypothalamus, but did not affect dopamine function. NmU markedly increased FLI in the nucleus accumbens, frontal cortex and central amygdala. CONCLUSIONS: These data provide further evidence for widespread roles for NmU and its receptors in the brain.