Knowledge, attitudes and self-confidence with skills required for providing dementia care in physicians at primary healthcare settings in Vietnam.

BACKGROUND: Dementia is a global public health priority. The World Health Organization adopted a Global Action Plan on Dementia, with dementia awareness a priority. This study examined the knowledge, attitudes, and self-confidence with skills required for providing dementia care among primary health care providers in Vietnam. METHODS: A cross-sectional study was conducted with 405 primary health care providers who worked at commune health stations and district health centers in eight provinces across Vietnam. RESULTS: The results showed that primary health care providers had poor knowledge and little confidence but more positive attitudes toward dementia care and management. CONCLUSIONS: The results suggest the training needs for building capacity amongst primary health care providers, which will be critical as Vietnam's population ages.

The effect of M. tuberculosis lineage on clinical phenotype.

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49-2.15), p<0.001; aOR = 1.40(1.09-1.79), p = 0.007; aOR = 2.04(1.65-2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57-0.83), p<0.001) and L4 strains (aOR = 0.73(0.59-0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.

The effect of M. tuberculosis lineage on clinical phenotype.

Eight lineages of Mycobacterium tuberculosis sensu stricto are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49-2.15), p<0.001; aOR=1.40(1.09-1.79), p=0.007; aOR=2.04(1.65-2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR=0.69(0.57-0.83), p<0.001) and L4 strains (aOR=0.73(0.59-0.90), p=0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p=0.033, p=0.008 and p=0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.

Urinary catecholamine excretion, cardiovascular variability, and outcomes in tetanus.

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay.

Metformin as adjunctive therapy in combination with multidrug treatment for multibacillary leprosy: A protocol for a randomized double-blind, controlled Phase 2 trial in Indonesia (MetLep Trial).

Background: The clinical management of leprosy is complicated by leprosy reactions (LR) causing irreversible nerve damage and disabilities. LR often require long-term use of corticosteroids causing serious side effects. Adjunct host-directed therapy (HDT) is a potentially attractive strategy in leprosy to prevent LR and associated immunopathology, modulate immunological memory that protects against recurrence, and thereby reduce nerve damage, disability and corticosteroid-associated morbidities. Metformin, a well-tolerated, safe and cheap anti-hyperglycaemic drug, is repurposed as HDT in auto-immune and infectious diseases, like tuberculosis (TB). Metformin use in people with diabetes is associated with reduced risks of TB-infection, progression to active TB, treatment failure and TB-mortality. Given the similarities both mycobacteria share, we hypothesize that among persons with multibacillary (MB) leprosy, adjunctive metformin may prevent/mitigate LR. Methods: We will perform a double-blind controlled proof-of-concept trial in which people with newly diagnosed multibacillary leprosy will be randomized (1:1) to metformin hydrochloride 1000mg extended release once daily versus placebo for 24 weeks in addition to standard-of-care WHO MB multidrug therapy (MDT) during 48 weeks. We aim to enrol 166 participants aged between 18 and 65 years, across five clinical sites in two leprosy endemic areas in Indonesia. Primary outcomes are the proportion of participants experiencing a LR and the frequency of (serious) adverse events. Secondary outcomes are the severity and time to first LR, the cumulative corticosteroid usage, and quality of life. The total study follow-up is 48 weeks. Discussion: LR signify the most important cause of irreversible nerve damage leading to anatomical deformities and disabilities, imposing a social and financial burden on those affected. Our study aims to evaluate the efficacy, tolerability and safety of adjunct metformin added to MDT in persons with multibacillary leprosy, and explore its effects on clinical and immunological outcomes. ClinicalTrialsgov registration: NCT05243654 (17/02/2022).

The metabolomic signatures of alcohol consumption in young adults.

BACKGROUND: Metabolomic analysis may help us to understand the association between alcohol consumption and cardio-metabolic health. We aimed to: (i) replicate a previous study of alcohol consumption and metabolic profiles, (ii) examine associations between types of alcoholic beverages and metabolites and (iii) include potential confounders not examined in previous studies. METHODS: Cross-sectional data of 1785 participants (age 26-36 years, 52% women) from the 2004-2006 Childhood Determinants of Adult Health study were used. Consumption of beer, wine and spirits was assessed by questionnaires. Metabolites were measured by a high-throughput nuclear magnetic resonance platform and multivariable linear regression examined their association with alcohol consumption (combined total and types) adjusted for covariates including socio-demographics, health behaviours and mental health. RESULTS: Alcohol consumption was associated with 23 out of 37 lipids, 12 out of 16 fatty acids and six out of 20 low-molecular-weight metabolites independent of confounders with similar associations for combined total alcohol consumption and different types of alcohol. Many metabolites (lipoprotein lipids in high-density lipoprotein (HDL) subclasses, HDL cholesterol, apolipoprotein A-1, phosphotriglycerides, total fatty acids, monounsaturated fatty acids, omega-3 fatty acids) had positive linear associations with alcohol consumption but some showed negative linear (low-density lipoprotein particle size, omega-6 fatty acids ratio to total fatty acids, citrate) or U-shaped (lipoprotein lipids in very-low-density lipoprotein (VLDL) subclasses, VLDL triglycerides) associations. CONCLUSIONS: Our results were similar to those of the only previous study. Associations with metabolites were similar for total and types of alcohol. Alcohol consumption in young adults is related to a diverse range of metabolomic signatures associated with benefits and harms to health.

Associations between alcohol consumption and cardio-metabolic risk factors in young adults.

Introduction The benefits of alcohol consumption for cardiovascular and metabolic health may have been overstated due to inappropriate comparisons with abstainers and inadequate control for confounding factors including physical activity and mental health. We examined alcohol consumption and cardio-metabolic health in a cohort of young Australian adults overcoming these limitations. Methods Cross-sectional data of a cohort of 2200 participants (age range 25-36 years) from the 2004-06 Childhood Determinants of Adult Health were used. Alcohol consumption was assessed from questionnaire and cardio-metabolic risk factors were measured in clinics. Linear and log binomial regression were used to examine total alcohol consumption (categories: none 0 g/day; light >0-10 g/day [reference]; moderate >10-20 g/day; heavy >20-30 g/day; very heavy >30 g/day) against dichotomous metabolic syndrome and its components: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure and glucose. Covariates included socio-demographics, smoking, diet, physical activity, fitness, depression and anxiety. Results Of the 2220 participants (48% males, mean (standard deviation) age 29.5 (2.5) years), most were classified in the 'light drinking' group (54.2%), less were in the 'non-drinking' (13.2%), 'heavy' (5.2%) or 'very heavy' (5.5%) drinking groups. Only moderate drinking was associated with a significantly lower prevalence of metabolic syndrome (prevalence ratio = 0.64, p < 0.05) compared with light drinking. Higher levels of alcohol consumption were associated with higher high-density lipoprotein cholesterol (ß = 0.05, ptrend < 0.001). Very heavy compared to light drinkers had higher systolic (ß = 3.01 mm Hg, p < 0.01) and diastolic (ß = 2.07 mm Hg, p < 0.05) blood pressure. Conclusion Moderate alcohol consumption was associated with a lower prevalence of MetS, and more favourable levels of lipids but not glucose or blood pressure even when compared to light consumption and with account for a range of confounding factors.