Mexiletine (NaMuscla) for the treatment of myotonia in non-dystrophic myotonic disorders

Introduction: NaMuscla, (mexiletine), is the first licensed treatment for the Non-Dystrophic Myotonias (NDM). NDM are categorized by genetic ion channel dysfunction and cause significant morbidity. To date, off-license mexiletine, although less costly, has sometimes been subject to breaches in supply causing significant regional and national variation in availability. Areas covered: The evidence supporting mexiletine use in NDM, its mechanism of action, chemistry, and pharmacodynamics is reviewed. The evidence for other, unlicensed medications, used to treat myotonia as well as new antimyotonic compounds in development is also reviewed. Expert opinion: Mexiletine is an effective and safe treatment for NDM. However, while mexiletine is very effective in reducing muscle stiffness, it is less effective at treating the pain associated with NDM and some SCN4A genotypes may not respond to mexiletine treatment. In addition, gastrointestinal discomfort is frequent and may prevent adequate dose titration. Since the designation of mexiletine as an orphan drug for NDM, level 1 evidence for the antimyotonic effect of lamotrigine has emerged. However, no superiority trials have been completed. A head-to-head trial to compare the efficacy of mexiletine and lamotrigine in reducing both muscle stiffness and pain and to determine variation in genotype response would facilitate greater precision medicine in NDM

Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited)

BACKGROUND: Cognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. AIM: We investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. METHODS: Carotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. RESULTS: People with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. CONCLUSIONS: This multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health

Occupancy of wild southern pig-tailed macaques in intact and degraded forests in Peninsular Malaysia

Deforestation is a major threat to terrestrial tropical ecosystems, particularly in Southeast Asia where human activities have dramatic consequences for the survival of many species. However, responses of species to anthropogenic impact are highly variable. In order to establish effective conservation strategies, it is critical to determine a species’ ability to persist in degraded habitats. Here, we used camera trapping data to provide the first insights into the temporal and spatial distribution of southern pig-tailed macaques (Macaca nemestrina, listed as ‘Vulnerable’ by the IUCN) across intact and degraded forest habitats in Peninsular Malaysia, with a particular focus on the effects of clear-cutting and selective logging on macaque occupancy. Specifically, we found a 10% decline in macaque site occupancy in the highly degraded Pasoh Forest Reserve from 2013 to 2017. This may be strongly linked to the macaques’ sensitivity to intensive disturbance through clear-cutting, which significantly increased the probability that M. nemestrina became locally extinct at a previously occupied site. However, no clear relationship between moderate disturbance, i.e. selective logging, and the macaques’ local extinction probability as well as site occupancy was found in the Pasoh Forest Reserve and Belum-Temengor Forest Complex. Further, an identical age and sex structure of macaques in selectively logged and completely undisturbed habitat types within the Belum-Temengor Forest Complex indicated that the macaques did not show increased mortality or declining birth rates when exposed to selective logging. Overall, this suggests that low to moderately disturbed forests may still constitute valuable habitats that support viable populations of M. nemestrina, and thus need to be protected against further degradation. Our results emphasize the significance of population monitoring through camera trapping for understanding the ability of threatened species to cope with anthropogenic disturbance. This can inform species management plans and facilitate the development of effective conservation measures to protect biodiversity

An Annotated Checklist Of Herpetofauna Of Langkawi Island, Kedah, Malaysia.

The herpetofauna ofLangkawi Island was recorded during the Scientific & Heritage Expedition ofthe Langkawi Islands, Kedah from 10 -15 April 2003. The reptiles such as snakes, lizards and turtles and amphibians such as toads and frogs were captured or observed and then identified. The reptiles and amphibians were captured and observed during trekking bouts along used and unused trails, along rivers and streams and during chance encounter

Multicultural Transitions: Caregiver Presence and Language-Concordance at Discharge

Introduction: Patients with low health literacy (HL) and minority patients encounter many challenges during hospital to community transitions. We assessed care transitions of minority patients with various HL levels and tested whether presence of caregivers and provision of language-concordant care are associated with better care transitions. Methods: A prospective cohort study of 598 internal medicine patients, Hebrew, Russian, or Arabic native speakers, at a tertiary medical center in central Israel, from 2013 to 2014. HL was assessed at baseline with the Brief Health Literacy Screen. A follow-up telephone survey was used to administer the Care Transition Measure [CTM] and to assess, caregiver presence and patient–provider language-concordance at discharge. Results: Patients with low HL and without language-concordance or caregiver presence had the lowest CTM scores (33.1, range 0–100). When language-concordance and caregivers were available, CTM scores did not differ between the medium-high and low HL groups (68.7 and 66.9, respectively, p = 0.118). The adjusted analysis, showed that language-concordance and caregiver presence during discharge moderate the relationship between HL and patients’ care transition experience ('p' < 0.001). Conclusions: Language-concordance care and caregiver presence are associated with higher patients’ ratings of the transitional-care experience among patients with low HL levels and among minorities

Activities forgone because of chronic breathlessness: a cross-sectional, population prevalence study

BackgroundChronic breathlessness is a prevalent, disabling syndrome affecting many people for years. Identifying the impact of chronic breathlessness on people’s activities in the general population is pivotal for designing symptom management strategies. ObjectiveThis study aimed to evaluate the association between chronic breathlessness and activities respondents identify can no longer be undertaken (‘activities foregone’). DesignThis population-based, cross sectional, online survey used a market research company’s database of 30,000 registrants for each sex, generating the planned sample size - 3,000 adults reflecting Australia’s 2016 Census by sex, age group, state of residence and rurality. Setting/Subjects The population of focus (n=583) reported a modified Medical Research Council (mMRC) breathlessness scale >1 and experienced this breathlessness for >3 months. MeasurementsActivities forgone were categorised by mMRC using coding derived from the Dyspnea Management Questionnaire domains. Activities were classified as ‘higher/lower intensity’ using Human Energy Expenditure scale.ResultsRespondents were: male 50.3%; median age 50.0 (IQR 29.0); with 66% living in metropolitan areas; reporting 1,749 activities forgone. For people with mMRC 1 (n=533), 35% had not given up any activity, decreasing to 9% for mMRC 2 (n=38) and 3% for mMRC 3-4 (n=12). Intense sport (e.g. jogging, bike riding) was the top activity forgone: 42% (mMRC 1); 32% (mMRC 2); and 36% (mMRC 3-4). For respondents with mMRC 3-4, the next most prevalent activities foregone were ‘sexual activities’ (14%); ‘lower intensity sports’ (11%) and ‘other activities’ (11%).ConclusionsPeople progressively reduce a wide range of activities because of their chronic breathlessness

Odontoid metastasis: a potential lethal complication

Nearly one third of cervical spine metastasis has a primary breast malignancy. Patients with cervical metastasis have higher mortality due to advanced stage of the malignancy. Treatment is palliative to relieve pain, prevent pathological fracture, improve mobility and function, and prolong survival. We describe a 40-year-old woman with a history of breast cancer who presented with neck and shoulder pain of 1 week duration with no neurological deficit. Following clinical examination, radiographs taken of the cervical spine was normal. Radiographs repeated 3 weeks later revealed a large lytic lesion of the odontoid occupying 70–80% of the peg. Further investigation including magnetic resonance imaging and bone scan showed no further spinal lesions. She underwent cyclical radiotherapy with complete resolution of the odontoid peg lesion and clinically was asymptomatic at 2 years. Metastatic lesions of the odontoid are atypical, and this case reinforces the necessity of early detection to evade disastrous consequences