METHODS: Altogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol-chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy-Weinberg equilibrium were also calculated.
RESULTS: Two SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race-stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD.
CONCLUSION: We found a significant association between SNP, which are located in autophagy-related genes, and CD in a Malaysian population.
METHODS: Prospectively enrolled patients with RAP and CP were followed up, and the alcoholic and idiopathic subgroups were assessed for progression of structural and functional changes in the organ.
RESULTS: One hundred and forty patients (RAP = 44; 31.4 %, CP = 96; 68.5 %) were followed up over a median 12.2 (interquartile range 12.0-16.8) months. The cause was alcohol in 31 (22.1 %) and not evident in 109 (77.8 %). The disease progressed from RAP to CP in 7 (15.9 %), 6 (16.2 %) out of 37 in the idiopathic and 1 (14.2 %; p = 1.00) out of 7 in the alcoholic subgroups. Three (42.8 %) and 1 (14.2 %) developed steatorrhea and diabetes mellitus (DM), respectively, and 2 (4.5 %) developed calcification. Established CP progressed in 19 (19.7 %), 1 (1.0 %), 5 (5.2 %), 2 (2.0 %) and 11 (11.4 %) newly developed DM, steatorrhea, calcification and duct dilation during follow up. Among the idiopathic and alcoholic CP, disease progression was seen in 15 (20.8 %) out of 72 and 4 (16.6 %) out of 24 respectively.
CONCLUSIONS: Idiopathic RAP and CP progressed during the short-term follow up. This is similar to other etiological forms of pancreatitis, as described from elsewhere in the world.
METHODS: We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide.
FINDINGS: Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016 was estimated to be substantially less than the recommended threshold to prevent outbreaks. Overall, we estimated that vaccination coverage levels achieved by 2016 avert between 94 336 and 118 500 cases of yellow fever annually within risk zones, on the basis of conservative and optimistic vaccination scenarios. The areas outside at-risk regions with predicted high receptivity to yellow fever transmission (eg, parts of Malaysia, Indonesia, and Thailand) were less extensive than the distribution of the main urban vector, A aegypti, with low receptivity to yellow fever transmission in southern China, where A aegypti is known to occur.
INTERPRETATION: Our results provide the evidence base for targeting vaccination campaigns within risk zones, as well as emphasising their high effectiveness. Our study highlights areas where public health authorities should be most vigilant for potential spread or importation events.
FUNDING: Bill & Melinda Gates Foundation.
METHOD: Between November 2009 and July 2010, outpatients from 45 countries who met the criteria for stable CAD were recruited into the registry. Baseline characteristics were documented at enrolment, and patients were reassessed during their annual visits over a five-year follow-up period. Key outcomes measured were sudden death and cardiovascular (CV) death, non-CV death and CV morbidity.
RESULTS: At baseline, 33,283 patients were available for analysis within the registry; 380 and 27 were Malaysians and Bruneians, respectively. The mean ages of Malaysian/Bruneian patients and the rest of the world (RoW) were 57.83 ±9.98 years and 64.23 ± 10.46 years, respectively (p<0.001). The median body mass index values were 26.6 (24.4-29.6) kg/m2 and 27.3 (24.8-30.3) kg/m2, respectively (p=0.014). Malaysian/Bruneian patients had lower rates of myocardial infarction (54.55% versus 59.76%, p=0.033) and higher rates of diabetes (43.24% versus 28.99%, p<0.001) and dyslipidaemia (90.42% versus 74.66%, p<0.001) compared with the RoW. Measured clinical outcomes in Malaysian and Bruneian patients at 2-years follow-up were low and generally comparable to the RoW.
CONCLUSION: Malaysian/Bruneian patients with stable CAD tend to be younger with poorer diabetic control compared with the RoW. However, they had similar outcomes as the main registry following two years of treatment.
BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016.
METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported.
RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful.
CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.