Respiratory measurements and airway clearance device prescription over one year in amyotrophic lateral sclerosis.

Objective: The rates of decline in respiratory measurements, including Peak Cough Flow (PCF) have not been established in Amyotrophic Lateral Sclerosis (ALS). Additionally, optimal prescription of cough adjuncts which aim to increase cough strength are unknown. The primary aim of this study was to quantify declines in respiratory function in ALS using PCF, Sniff Nasal Inspiratory Pressure (SNIP) and Slow Vital Capacity (SVC). Secondary aims were to measure respiratory morbidity, audit the characteristics of those prescribed cough adjuncts, and compare outcomes between treated and untreated cohorts. Methods: A prospective, longitudinal, observational, cohort study evaluated respiratory measures, morbidity, and physical function in ALS patients at three monthly intervals, over one year. Patient and disease characteristics of those prescribed cough adjuncts were profiled at the time of device prescription. Results: one hundred and eight participants with mean age 62.1 ± 11.5 years participated. PCF declined rapidly at a rate of 124.8L/min/year (p < 0.001). SNIP, SVC (%predicted), and ALSFRS-R also declined significantly at rates of 18.72cmH2O, 17.49%, and 9.62 units per year respectively (p < 0.001). Thirty-two (29.6%) patients reported 56 incidences of chest infection and 21 died. Patients prescribed a cough adjunct (44.4%) had significantly lower average PCF, SNIP, SVC percent predicted, and ALSFRS-R (p < 0.001). Conclusions: This study identified a rapid rate of decline in PCF, a similar decline in SNIP, and slower declines in SVC and ALSFRS-R. Cough adjunct prescription was triggered by declining respiratory measures and recommended PCF thresholds, but also by respiratory symptoms. Chest infections were common in patients regardless of cough adjunct prescription and should be closely monitored.

Patient journey to a specialist amyotrophic lateral sclerosis multidisciplinary clinic: an exploratory study.

BACKGROUND: The multidisciplinary approach in the management of Amyotrophic Lateral Sclerosis (ALS) has been shown to provide superior care to devolved care, with better survival, improved quality of care, and quality of life. Access to expert multidisciplinary management should be a standard for patients with ALS. This analysis explores the patient journey from symptom onset and first engagement with health services, to the initial visit to a specialist ALS Multidisciplinary Clinic (MDC) in Dublin, Ireland. METHODS: A retrospective exploratory multi-method study details the patient journey to the MDC. Data from medical interviews and systematic chart review identifies interactions with the health services and key timelines for thirty five new patients presenting with a diagnosis of ALS during a 6 month period in 2013. RESULTS: The time from first symptom to diagnosis was a mean of 16 months (median 13 months), with a mean interval of 19 months (median 14.6) from first symptoms to arrival at the MDC. The majority of patients were seen by a general practitioner, and subsequently by neurology services. There was an average of four contacts with health services and 4.8 investigations/tests, prior to their first Clinic visit. On the first visit to the MDC patients are linked into an integrated 'system' that can provide specialist care and link with voluntary, palliative and community services as required. CONCLUSIONS: Engagement with a multidisciplinary team has implications for service utilization and quality of life of patients and their families. We have demonstrated that barriers exist that delay referral to specialist services. Comprehensive data recording and collection, using multiple data sources can reconstruct the timelines of the patient journey, which can in turn be used to identify pathways that can expedite early referral to specialist services.

Oxysterols and Alzheimer's disease.

There is a clear link between cholesterol turnover and neurodegenerative diseases and hypercholesterolemia is an established risk factor for Alzheimer's disease (AD). The failure to demonstrate a transfer of cholesterol from the circulation into the brain in humans and experimental animals makes it difficult to explain the link between hypercholesterolemia and AD. In contrast to cholesterol itself, side-chain oxidized cholesterol metabolites such as 24S-hydroxycholesterol and 27-hydroxycholesterol are able to pass the blood-brain barrier (BBB). Formation of 24S-hydroxycholesterol is the quantitatively most important mechanism for elimination of cholesterol from the brain and we recently demonstrated a significant net uptake of 27-hydroxycholesterol by the brain from the circulation. We have also shown that patients with AD have increased brain levels of 27-hydroxycholesterol, which may affect the production of beta-amyloid in the brain. The levels of 27-hydroxycholesterol in the circulation are correlated with the levels of cholesterol and the possibility must be considered that the flux of 27-hydroxycholesterol into the brain is the missing link between hypercholesterolemia and Alzheimer's disease. Current knowledge about the role of the two oxysterols for cholesterol homeostasis in the brain as well as their diagnostic potential are reviewed.