Genetic and Environmental Contributors to Neurodegeneration: An Exploration of the Effects of Alcohol on Clinical Features of Huntington’s Disease Using the Enroll-HD Global Platform

Huntington’s disease (HD) is a neurodegenerative dementia with a well recognised genetic cause. Alcohol misuse is a major environmental factor relevant to numerous neurological presentations, including HD. We explored the effects of alcohol intake on clinical features of HD by means of data from the Enroll-HD, which is a global registry study. A retrospective observational study making use of the Enroll-HD periodic dataset up to 2020 (in accordance with the Enroll-HD guidelines, encompassing 16,120 subjects with the HD gene (CAG expansion > 36), was carried out. This included 180 sites in 21 countries. The study looked at the association of alcohol use with the clinical presentation of HD, specifically looking into the age of first symptoms and HD severity. We also describe a specific case with manifest HD, a participant in the Enroll-HD study, whereby the patient’s obsessionality was central to her pattern of high alcohol intake and to her successful avoidance of alcohol thereafter. A record of past problems with high alcohol intake was more common in the group with manifest HD (9.0%, n = 1121) when compared with the pre-manifest carriers of the HD genetic abnormality (2.3%, n = 339). Age at onset of symptoms was not significantly influenced by current alcohol misuse, or past misuse. The severity of clinical impairments in HD was influenced by alcohol. Patients who reported high alcohol intake in the past had a statistically significant increase in motor impairments, by the Unified Huntington’s Disease Rating Scale total motor score (Kruskal–Wallis, post hoc Dunn’s, p < 0.001), and a significantly higher burden of psychiatric symptoms by the Problem Behaviours Assessment score (Kruskal–Wallis, post hoc Dunn’s, p < 0.01) compared with those not reporting high alcohol use. However, the past alcohol group did not have a lower Mini Mental State Examination score (Kruskal–Wallis, post hoc Dunn’s, p > 0.05) The first symptom of HD, as determined by the assessing clinician, was more likely to be psychiatric disturbance in patients currently misusing alcohol or those with prior history of alcohol misuse (55% and 31% respectively) when compared with controls (5%). Individual case experience, such as that presented in this study, shows that HD and alcohol, two major genetic and environmental contributors to neurodegeneration, interact in producing clinical problems. However, the complexities of these interactions are difficult to define, and may require larger studies dedicated to exploring the various factors in this interaction.

Economic burden of noncommunicable diseases attributable to risk factors in the Russian Federation

Aim to estimate the economic burden of major chronic noncommunicable diseases (NCDs) attributable to risk factors in the Russian Federation in 2016 Material and Methods The following risk factors were included in the analysis: smoking, high alcohol intake, high salt intake, low intake of fresh vegetables and fruits, consumption of processed red meat, low physical activity, obesity, hypertension, which reliably have a causal relationship with major NCDs: cardiovascular diseases(CVD),type 2 diabetes, chronic obstructive pulmonary disease(COPD), cancer of 10 localizations. The relative risks (RR)of morbidity and mortality from major NCDs associated with risk factors are identified through a literature search. Based on the data on the prevalence of risk factors in the Russian population and RR, the population attributable risk (PAR)was calculated for each analyzed disease. Statistical analysis calculations using descriptive statistics methods were performed in the MSExcel 10.0 program. Results The largest burden from the four main NCDs is associated with hypertension - 10.9 billion€, which is equivalent to 1.01% of GDP. The next largest contribution to the burden from NCDs was the burden from obesity 7.6 billion€ 0.7% of GDP, smoking over 5.2 billion €, 0.49% of GDP and the low physical activity 3.4 billion€, 0.32% of GDP. Of all the analyzed risk factors, the least contribution to total costs in connection with NCDs was determined by the burden from high alcohol intake 1.1 billion€, 0.1% of GDP, due to the low prevalence of high alcohol intake in the Russian population. Conclusions In this study, for the first time, the assessment of the economic burden of risk factors by the share (contribution) to the morbidity and mortality of main NCDs (CVD, T2DM, COPD and 10 cancer localizations) in the Russian Federation for 2016 was performed. Such the significant economic burden is a strong argument for increasing investments in the prevention and treatment of risk factors of NCDs. Key messages In Russia the largest burden from the four main NCDs is associated with hypertension. Such the significant economic burden is a strong argument for increasing investments in the prevention and treatment of risk factors of NCDs.

Evaluation of Risk Factors for Hepatotoxicity in Patients Receiving Antitubercular Four Drugs Regimen in Initial Two Months

Background: Tuberculosis (TB) is a major public health problem in Bangladesh since long before. Standard first line drugs are isoniazid, rifampicin, pyrazinamide and ethambutol. Of these, isoniazid, rifampicin and pyrazinamide have been observed to have hepatotoxic potentials. Drug Induced Hepatotoxicity (DIH) is an important and commonly encountered adverse effect with anti-TB treatment. A higher risk of hepatotoxicity has been reported in Bangladeshi patients than in their western counterparts. The reasons for the higher rate of hepatotoxicity in Bangladeshi patients are unclear. Objectives: To know the possible risk factors for the development of drug induced hepatotoxicity and to see their association with hepatoxicity in patients receiving antitubercular treatment as per National Tuberculosis Control Programme. Materials and Methods: In this cross sectional prospective study, 100 freshly diagnosed pulmonary tuberculosis patients attending the Medicine Outpatient Department, admitted in Chittagong Medical College Hospital, DOTS center in the hospital were selected for the study. Results: In this study we found twenty percent patients (20%) developed Antituberculosis Treatment (ATT) induced hepatotoxicity and most of them were in the age group of 50–65 years. Among the patients who developed hepatotoxicity (DIH) 27% patients were in BMI 18.5 group. The patients presenting with radiologically severe Pulmonary Tuberculosis (PTB) developed higher hepatotoxicity than patients with milder disease. The patients with history of high alcohol intake and with pre-treatment hypoalbuminemia were also found to have higher drug induced hepatotoxicity as compared to non-alcoholics and normal serum albumin level respectively. This study showed the evidence of ATT induced liver damage in twenty percent (20%) patients. Among them 05% cases developed overt drug induced hepatotoxicity (DIH) and remaining 15% cases had asymptomatic elevation of serum ALT, AST and bilirubin levels. The remaining 80% cases did not show any significant change in their serum bilirubin and/or enzyme levels as compared to pre-treatment levels. Conclusion: Advanced age, high alcohol intake, radiologically severe disease before treatment and pretreatment hypoalbuminemia are predisposing factors for the development of ATT induced hepatotoxicity.DOI: http://dx.doi.org/10.3329/cmoshmcj.v14i1.22873 Chatt Maa Shi Hosp Med Coll J; Vol.14 (1); Jan 2015; Page 15-18

Population-attributable risks for modifiable lifestyle factors and breast cancer in New Zealand women.

15 Background: Breast cancer is an important cause of illness and death in New Zealand women. It is the most commonly registered cancer in women, and the second most common cause of cancer death in women. In 2009, 2,759 women were diagnosed with breast cancer and 658 women died from breast cancer. The incidence of breast cancer is projected to stabilise in New Zealand, but the actual number of women diagnosed with breast cancer will increase because of the increasing proportion of older people and increasing size of the population. Methods: Estimates of the magnitude of modifiable lifestyle risk factors for breast cancer (relative risks and odds ratios obtained from published epidemiological studies) and the prevalence of exposure in New Zealand were used to calculate the population attributable risk percent (PAR%) for each risk factor. The PAR%s show the relative importance of these risk factors, and give an indication of the potential impact of reducing the prevalence of these lifestyle risk factors on the incidence of breast cancer in New Zealand. Results: Six modifiable lifestyle factors were identified for breast cancer. These were obesity, lack of physical activity, high alcohol intake, oral contraceptive use, hormone replacement therapy (HRT), and delayed first birth. The PAR%s for these risk factors ranged from 1% for delayed first birth to 10% for obesity (16% for Maori women and 17% for Pacific women). Conclusions: The most important primary preventive strategies to reduce the risk of breast cancer in New Zealand are promoting lifestyle changes to reduce obesity, promoting regular physical activity (which may in turn reduce the prevalence of obesity), reducing HRT use, and avoiding high alcohol intake. A strategy to promote regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.