Biomedical subjects

B J Traynor

Publications and source records attributed to B J Traynor.

10 recordsLinked to original sources

PubMed2006

Neuroprotective agents for clinical trials in ALS: a systematic assessment.

BACKGROUND: Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest. OBJECTIVE: To identify potential neuroprotective agents for testing in phase III clinical trials and to outline which data need to be collected for each drug. METHODS: The authors identified 113 compounds by inviting input from academic clinicians and researchers and via literature review to identify agents that have been tested in ALS animal models and in patients with ALS. The list was initially narrowed to 24 agents based on an evaluation of scientific rationale, toxicity, and efficacy in previous animal and human studies. These 24 drugs underwent more detailed pharmacologic evaluation. RESULTS: Twenty drugs were selected as suitable for further development as treatments for patients with ALS. Talampanel and tamoxifen have completed early phase II trials and have demonstrated preliminary efficacy. Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS. Remaining agents (AEOL 10150, arimoclomol, celastrol, coenzyme Q10, copaxone, IGF-1-viral delivery, memantine, NAALADase inhibitors, nimesulide, scriptaid, sodium phenylbutyrate, thalidomide, trehalose) require additional preclinical animal data, human toxicity and pharmacokinetic data including CNS penetration prior to proceeding to large scale phase III human testing. Further development of riluzole analogues should be considered. CONCLUSIONS: Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2004

A novel candidate region for ALS on chromosome 14q11.2.

Sequence variations with biologic effect in ALS have been identified in the gene for vascular endothelial growth factor (VEGF). The gene for a related protein, angiogenin, lies on chromosome 14q11.2. Analysis of the angiogenin (ANG) gene in the authors' population has demonstrated a significant allelic association with the rs11701 single nucleotide polymorphism (SNP) and identified a novel mutation in two individuals with sporadic ALS that potentially inhibits angiogenin function. These observations propose a candidate region for ALS on chromosome 14q11.2 and suggest that other genes with similar function to VEGF may be important in the pathogenesis of ALS.

Aged↗

PubMed2004

Functional outcome measures as clinical trial endpoints in ALS.

The topiramate study was a 12-month randomized placebo-controlled trial in patients with ALS. Follow-up evaluation of the placebo group (n = 97) constituted a well-described cohort of patients with ALS, in whom multiple outcome measures were assessed at 3-month intervals. During the 12-month study period, the decline of forced vital capacity (FVC%) and ALS functional rating scale (ALSFRS) was linear, whereas the decline of maximum voluntary isometric contraction-arm (MVIC-arm) and MVIC-grip Z scores was curvilinear. Rates of FVC% and ALFRS decline, but not of MVIC-arm or MVIC-grip, were independent predictors of survival.

Adult↗

PubMed2003

Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000.

BACKGROUND: In recent years, there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis (ALS) patients with the emergence of multidisciplinary ALS clinics that cater exclusively for patients with this condition. The impact of multidisciplinary management has not been previously evaluated. METHODS: Using data from the Irish ALS Register, we conducted a prospective, population based study of all ALS cases diagnosed in Ireland over a five year period to evaluate the effectiveness of a multidisciplinary clinic on ALS survival. RESULTS: Eighty two (24%) patients attended the multidisciplinary ALS clinic, with the remaining 262 (76%) cases followed in a general neurology clinic. The ALS clinic cohort was an average of five years younger (60.1 v 65.6 years) and were more likely to receive riluzole than the general neurology cohort (99% v 61%). The median survival of the ALS clinic cohort was 7.5 months longer than for patients in the general neurology cohort (logrank = 15.4, p < 0.0001). Overall, one year mortality was decreased by 29.7%. Prognosis of bulbar onset patients was extended by 9.6 months if they attended the ALS clinic. Using multivariate analysis, attendance at the ALS clinic was an independent covariate of survival (HR = 1.47, p = 0.02). CONCLUSIONS: ALS patients who received their care at a multidisciplinary clinic had a better prognosis than patients attending a general neurology clinic. The data suggest that active and aggressive management enhances survival, particularly among ALS patients with bulbar dysfunction. The effect of clinic type must be considered in future clinical trials design.

Adult↗

PubMed2000

Amyotrophic lateral sclerosis mimic syndromes: a population-based study.

BACKGROUND: The Irish ALS Register is a population-based register of the epidemiological characteristics of amyotrophic lateral sclerosis (ALS) in the republic of Ireland. OBJECTIVE: To describe the clinical and demographic details of those patients included in the Irish ALS Register who were incorrectly diagnosed as having ALS (patients who were ultimately rediagnosed as having an "ALS mimic syndrome"). METHODS: The medical records of each patient referred to the register are routinely reviewed and, where possible, patients are examined by our group during their illness. RESULTS: Between January 1, 1993, and December 31, 1997, 32 patients (representing 7.3% of 437 referrals) were rediagnosed as having a condition other than ALS. The median age at onset for these 32 patients was 56.0 years (range, 19.5-85.8 years) for men and 53.5 years (range, 39.5-70.4 years) for women. Twenty-nine patients (91%) presented with symptoms referable to the limbs, and the remainder presented with symptoms involving the bulbar musculature. Multifocal motor neuropathy was the most common condition mistaken for ALS, accounting for 7 cases (22%), followed closely by Kennedy disease (4 cases [13%]). Factors leading to diagnostic revision included evolution of atypical symptoms, results of specific investigations, and failure of symptoms to progress. Twenty-seven (84%) of the patients with an ALS mimic syndrome fulfilled the El Escorial criteria for either "suspected" or "possible" ALS, 4 (13%) met the criteria for probable ALS, and 1 (3%) had definite ALS. CONCLUSIONS: The application of the El Escorial diagnostic criteria may facilitate early recognition of non-ALS cases. Misdiagnosis of ALS remains a common clinical problem despite the increased availability of investigations and a greater awareness among neurologists of potential diagnostic pitfalls.

Adult↗

PubMed2000

Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study.

BACKGROUND: The El Escorial and the revised Airlie House diagnostic criteria for amyotrophic lateral sclerosis (ALS) classify patients into categories reflecting different levels of diagnostic certainty. We conducted a prospective, population-based study of the natural course of ALS in the Republic of Ireland during a 6-year period to examine the utility of these ALS diagnostic criteria. METHODS: Using data from the Irish ALS Register, we studied the clinical features of all patients diagnosed as having ALS in Ireland throughout their illness. RESULTS: Between 1993 and 1998, 388 patients were diagnosed as having ALS. Forty percent of patients reported bulbar-onset symptoms. Disease progression occurred over time: at last follow-up, 75% of all patients had bulbar signs, compared with 59% at diagnosis. When the El Escorial criteria were applied, more than half of patients (218 [56%]) had definite or probable ALS at diagnosis. Of the 165 possible and suspected ALS cases at diagnosis (trial ineligible), 110 (67%) were trial eligible at last follow-up. Of the 254 patients who had died, 229 (90%) had definite or probable ALS, whereas 25 patients (10%) remained trial ineligible at death. El Escorial category at diagnosis was not a significant prognostic indicator. Use of the Airlie House criteria had no effect on the median time from symptom onset to trial eligibility (12.9 vs 12.8 months). CONCLUSIONS: The El Escorial and Airlie House diagnostic criteria are excessively restrictive. Furthermore, levels of diagnostic certainty cannot be used as prognostic indicators. Arch Neurol. 2000;57:1171-1176

Adult↗

PubMed1999

Incidence and prevalence of ALS in Ireland, 1995-1997: a population-based study.

BACKGROUND: We conducted a prospective, population-based study of ALS in the Republic of Ireland for the 3-year period 1995 to 1997. METHODS: To ensure complete case ascertainment, multiple sources of information were used, including consultant neurologists, neurophysiologists, primary care physicians, and the Irish Motor Neuron Disease Association. The El Escorial diagnostic criteria for ALS were applied to all cases enrolled on the register and each patient was regularly followed up during his or her illness. RESULTS: Between January 1, 1995, and December 31, 1997, 231 patients were diagnosed with possible, probable, or definite ALS, including 133 men (57.6%) and 98 women (42.4%). The average annual incidence rate was 2.1 per 100,000 person-years (95% CI, 1.8 to 2.4), and 2.8 per 100,000 person-years for the population older than 15 years (95% CI, 2.4 to 3.1). The incidence rate was higher for men, being 2.5 per 100,000 person-years (95% CI, 2.0 to 2.9), than for women, at 1.8 per 100,000 person-years (95% CI, 1.5 to 2.2), and increased with age for both sexes. The median age at onset was 64.2 years for men and 67.8 years for women. On December 31, 1996, the crude prevalence was 4.7 per 100,000 of the total population (95% CI, 4.0 to 5.5), and 6.2 per 100,000 for the population older than 15 years (95% CI, 5.3 to 7.1). Adjusting to the 1996 Irish population as standard, the incidence of ALS in Ireland during the 3-year study period is the third highest reported to date. CONCLUSIONS: There was a trend toward a higher incidence of ALS in the northwestern region of Ireland, although the numbers of cases involved were small and further study is required.

Age Distribution↗

PubMed1998

Status epilepticus.

Explore the source record for details and available documents.

Diagnosis, Differential↗

PubMed1998

Service provision for patients with ALS/MND: a cost-effective multidisciplinary approach.

Optimal management of patients with ALS/MND requires a team approach, with early referral to paramedical services for clinical assessment and prompt intervention. As the condition progresses, a flexible approach to management must be adopted by the medical team, with an ability to intervene at very short notice. We have developed an efficient multi-disciplinary clinic that services the ALS/MND population of Ireland by combining the existing infrastructure of community services with a hospital-based specialist clinic. The clinic operates on a weekly basis, and is staffed by a core team including a neurologist, a liaison nurse, and the director of the ALS/MND Association. On-site and same-day physiotherapy, occupational therapy and speech therapy is available, as is pulmonary evaluation. All patients utilising the clinical services are automatically included on the Irish Register of Motor Neurone Disease, and are tracked by the liaison nurse. The core members of the clinic interact regularly with paramedical staff within the community, ensuring that necessary community services are made available within 1-2 weeks of the clinic visit. Equipment necessary for the patient's well being is made available free of charge by the Irish Motor Neurone Disease Association, following an appropriate request from the regional para-medical staff. We have thus demonstrated that an effective multi- disciplinary care service for ALS/MND can be developed at modest cost by close personal liaison between the existing health care structures and core members of a multidisciplinary team.

Amyotrophic Lateral Sclerosis↗

PubMedDate not supplied

Access to health services in Ireland for people with Multiple Sclerosis and Motor Neurone Disease.

We conducted a telephone questionnaire to determine the utilisation of hospital and community based services by patients with Motor Neurone Disease and Multiple Sclerosis in Ireland. 94 MND and 188 MS patients participated in the study. MND patients were more likely to have free medical care than MS patients, despite legislation favouring the converse. Severely disabled MND patients were more successful at accessing free community-based services than were severely disabled MS patients. Private medical insurance conferred no advantage when obtaining services or purchasing equipment. Many patients were unaware of the specific roles of the various clinical professionals. There are significant deficiencies in patients' ability to access multidisciplinary services. Voluntary organisations often bridge the gap in service provision. An investment in services for people with chronic neurological disability is urgently required.

Community Health Services↗