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Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
The aim of this study was to examine the gender differential effects of eating habits and physical activity on overweight and obesity among school-aged adolescents in Bangladesh. Nationally representative data extracted from the 2014 Global School-based Student Health Survey (GSHS) were utilized. The survey collected information related to physical and mental health from 2989 school-aged adolescents in Bangladesh. An exploratory data analysis and multivariate logistic regression model were employed in this study. Female adolescents were at a lower risk of being overweight or obese (AOR=0.573) than males, with a prevalence of 7.4% (males: 9.9%). The results showed that high consumption of vegetables (both: AOR=0.454; males: AOR=0.504; females: AOR=0.432), high soft drink consumption (both: AOR=2.357; males: AOR=2.929; females: AOR=1.677), high fast food consumption (both: AOR=2.777; males: AOR=6.064; females: AOR=1.695), sleep disturbance (both: AOR=0.675; males: AOR=0.590; females: AOR=0.555) and regular walking or cycling to school (both: AOR=0.472; males: AOR=0.430; females: AOR=0.557) were vital influencing factors for being overweight or obese among adolescents for both sexes. Sedentary activities during leisure time were also identified as significant predictors of being overweight or obese for males. Regular fruit and vegetable consumption, the avoidance of soft drinks and fast food, an increase in vigorous physical activity, regular attendance at physical education classes and fewer sedentary leisure time activities could all help reduce the risk of being overweight or obese for both sexes.
Introduction: In addition to its clinical utility, the Canadian Triage and Acuity Scale (CTAS) has become an administrative metric used by governments to estimate patient care requirements, emergency department (ED) funding and workload models. The electronic Canadian Triage and Acuity Scale (eCTAS) initiative aims to improve patient safety and quality of care by establishing an electronic triage decision support tool that standardizes that application of national triage guidelines across Ontario. The objective of this study was to evaluate triage times and score agreement in ED settings where eCTAS has been implemented. Methods: This was a prospective, observational study conducted in 7 hospital EDs, selected to represent a mix of triage processes (electronic vs. manual), documentation practices (electronic vs. paper), hospital types (rural, community and teaching) and patient volumes (annual ED census ranged from 38,000 to 136,000). An expert CTAS auditor observed on-duty triage nurses in the ED and assigned independent CTAS in real time. Research assistants not involved in the triage process independently recorded triage time. Interrater agreement was estimated using unweighted and quadratic-weighted kappa statistics with 95% confidence intervals (CIs). Results: 1491 (752 pre-eCTAS, 739 post-implementation) individual patient CTAS assessments were audited over 42 (21 pre-eCTAS, 21 post-implementation) seven-hour triage shifts. Exact modal agreement was achieved for 567 (75.4%) patients pre-eCTAS, compared to 685 (92.7%) patients triaged with eCTAS. Using the auditor's CTAS score as the reference standard, eCTAS significantly reduced the number of patients over-triaged (12.0% vs. 5.1%; Δ 6.9, 95% CI: 4.0, 9.7) and under-triaged (12.6% vs. 2.2%; Δ 10.4, 95% CI: 7.9, 13.2). Interrater agreement was higher with eCTAS (unweighted kappa 0.89 vs 0.63; quadratic-weighted kappa 0.91 vs. 0.71). Research assistants captured triage time for 3808 patients pre-eCTAS and 3489 post implementation of eCTAS. Median triage time was 312 seconds pre-eCTAS and 347 seconds with eCTAS (Δ 35 seconds, 95% CI: 29, 40 seconds). Conclusion: A standardized, electronic approach to performing CTAS assessments improves both clinical decision making and administrative data accuracy without substantially increasing triage time.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them
Introduction: In addition to its clinical utility, the Canadian Triage and Acuity Scale (CTAS) has become an administrative metric used by governments to estimate patient care requirements, ED funding and workload models. The Electronic Canadian Triage and Acuity Scale (eCTAS) initiative aims to improve patient safety and quality of care by establishing an electronic triage decision support tool that standardizes the application of national triage guidelines (CTAS) across Ontario. The objective of this study was to evaluate the implementation of eCTAS in a variety of ED settings. Methods: This was a prospective, observational study conducted in 7 hospital EDs, selected to represent a mix of triage processes (electronic vs. manual), documentation practices (electronic vs. paper), hospital types (rural, community and teaching) and patient volumes (annual ED census ranged from 38,000 to 136,000). An expert CTAS auditor observed on-duty triage nurses in the ED and assigned independent CTAS in real time. Research assistants not involved in the triage process independently recorded the triage time. Interrater agreement was estimated using unweighted and quadratic-weighted kappa statistics with 95% confidence intervals (CIs). Results: 1200 (738 pre-eCTAS, 462 post-implementation) individual patient CTAS assessments were audited over 33 (21 pre-eCTAS, 11 post-implementation) seven-hour triage shifts. Exact modal agreement was achieved for 554 (75.0%) patients pre-eCTAS, compared to 429 (93.0%) patients triaged with eCTAS. Using the auditors CTAS score as the reference standard, eCTAS significantly reduced the number of patients over-triaged (12.1% vs. 3.2%; 8.9, 95% CI: 5.7, 11.7) and under-triaged (12.9% vs. 3.9%; 9.0, 95% CI: 5.9, 12.0). Interrater agreement was higher with eCTAS (unweighted kappa 0.90 vs 0.63; quadratic-weighted kappa 0.79 vs. 0.94). Research assistants captured triage time for 4403 patients pre-eCTAS and 1849 post implementation of eCTAS. Median triage time was 304 seconds pre-eCTAS and 329 seconds with eCTAS ( 25 seconds, 95% CI: 18, 32 seconds). Conclusion: A standardized, electronic approach to performing CTAS assessments improves both clinical decision making and administrative data accuracy without substantially increasing triage time.
The pathogenesis of complex visual hallucination in patients without visual lesions, appearing with eyes open and resolving with eyes closed, has been described to be associated with increased excitation at the lateral geniculate nucleus (LGN) and pulvinar of the thalamus (Winton-Brown, 2016). This reduces thefidelity of retinogeniculate transmissions and enhances aberrant projections to the visual cortex. Loss of the central sensory filtering function of the pulvinar increases “signal to noise ratio” in visual transmission. While visual hallucinations have been reported to disappear on eye closure (Manford, 1998), visual aberration with correction with refractionfollowed by focusing on actual visual images and visual hallucinations has not heretofore been reported. Such a case is presented.
Case study: This 28-year-old, myopic, right-handed man, at 5 years of age began hallucinating vivid images of people. The visual hallucinations were triggered only with his eye open. He was myopic and without visual correction, his visual sphere would be blurred. The visual hallucinations were also blurred without visual correction. With refraction, the hallucinations became clearly in focus. He would close his eyes and the visual hallucinations disappeared but would reappear in the same position upon opening his eyes. For over 20 years, he experienced about 100 hallucinations a day. Electroencephalography (EEG) revealed continuous spikes and slow waves in bilateral temporal lobes, consistent with temporal lobe status epilepticus. After treatment with diphenylhydantoin the frequency and duration of the hallucinations markedly decreased to a second epoch every other day. However, the characteristic of the hallucinations remained the same (people).
This phenomenon may involve epilepsy induced excitation of the thalamus. This then acts to reduce the fidelity of retinogeniculate transmission and increase “signal to noise ratio” in visual transmission. This may contribute to complex visual hallucinations with eyes open. The hallucinated figures becoming clearer with eyeglasses provides support that this complex hallucination arises in the pathway from retina-LGN-cortex, not from stored visual associated cortex of top-down cortical release.
Given the above, those with visual hallucinations should be queried as to the influence of refraction on the clarity of hallucination.
Endogenous melatonin is a hormone secreted by pineal gland; it has several roles in metabolism, reproduction, and remarkable antioxidant properties. Studies on the melatonin effect on the adrenal glands which are important endocrine organs, controlling essential physiological functions, are still deficient. In this study, we attempted to investigate the effect of exogenous melatonin treatment on the adrenal cortex and medulla using several approaches. Adrenal glands of 15 Soay ram were examined to detect the effect of melatonin treatment. Our results revealed that the cells of adrenal cortex of the treated animals were separated by wide and numerous blood sinusoids and showed signs of increase steroidogenic activity, which are evidenced by functional hypertrophy with increase profiles of mitochondria, smooth endoplasmic reticulum, and lipid droplets. The most striking ultrastructural features in the medulla of the treated group were the engorgement of chromaffin cells with enlarged secretory granules enclosed within a significantly increased diameter of these cells. The cytoplasm of these cells showed numerous mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, lysosomes, and glycogen granules. Exocytosis of secretory granules to the lumen of blood vessels was evident in the treated group. Piecemeal degranulation mode of secretion was recorded after melatonin treatment. Chromaffin cells in the control group expressed moderate immunoreactivity to Synaptophysin and tyrosine hydroxylase, compared with intensified expression after melatonin treatment. The ganglion cells of the melatonin-treated group showed a significant increase in diameter with numerous rER. The most interesting feature in this study is the presence of small granule chromaffin cells (SGC) and telocytes (TCs) for the first time in the adrenal glands of sheep. Moreover, these SGC cells, Schwann cells, fibroblasts, and progenitor stem cells showed a stimulatory response. The TCs were small branched cells scattered in the adrenal glands around cortical cells, chromaffin cells, nerve fibers, and blood vessels. These cells increased significantly in number, length of their telopodes, and secretory activity after melatonin treatment. In addition, multiple profiles of unmyelinated nerve fibers were demonstrated in all treated specimens. These results indicated that melatonin treatment caused a stimulatory action on all cellular and neuronal elements of the adrenal gland. This study may act as a new direction for treatment of adrenal insufficiency.
Unavailability of irrigation water for early sowing has remained a constant problem in cold arid deserts of Ladakh. In order to get a solution to this problem, a 2-yr farmers’ participatory research trial with best bet agronomic management on artificial glacier water harvesting technology was conducted. The technology involves collecting water from natural glaciers that melt during late December. The water is diverted toward a shed constructed with stone embankments set up at regular intervals. The area is chosen where there is minimum interference of solar radiation, generally between two mountain slopes or ridge that is on the leeward side. The melted water is that melts from the natural glacier impeded by the embankments and get frozen here. This frozen water starts melting in late March and is used for both pre sowing and initial crop water requirement. It also ensures early sowing of wheat by creating additional 45-day window which leads to introduction of long- and medium-duration wheat varieties to replace decades old locally grown short-duration varieties. The work was initiated with a benchmark survey of 100 farmers to get an understanding of present irrigation scenario, crop management practices and date of sowing. Data from 99 farmer participating trial of wheat conducted after or from bench mark survey clearly indicated that the effect of water shortage can be seen on yield and yield attributing characters due to unavailability of pre sowing irrigation and water requirement at imperative growth stages and may also lead to terminal heat stress in wheat crop. Out of total number of irrigations applied, initial two irrigations can be compensated by artificial glacier water harvesting technique, leading to a revolution in the agriculture scenario of the tribal population by introduction of long- and medium-duration wheat varieties in cold arid desert of Ladakh for the very first time. It was observed that wheat seeding done in first fortnight of April gave better yields in comparison to late seeded wheat. Moreover, the long-duration varieties (LDVs) or medium-duration varieties (MDVs) sown under late condition gave better yield in comparison to locally grown short-duration varieties sown at same time. Yield potential of LDVs and MDVs of wheat under late sowing was found quite low in comparison to early-sown wheat, still when compared with the performance of locally grown wheat the yields were more even if the local varieties were sown early. The outcome of this study will help the farmers of tribal, cold arid community in harvesting better wheat yields by timely sowing of the wheat crop accompanied with better bet agronomic management practices. Government initiative is further required to ensure better outreach of complete crop management strategies to the tribal farming community of the region in order to ensure food security and improve their socioeconomic status.
Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline.
We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0–9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function).
At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1–4) and 226 (8%) men with moderate/severe symptoms (GAS 5–9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88).
In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.
Spatial confinement effects on plasma parameters and surface morphology of laser-ablated Mg are studied by introducing a metallic blocker as well as argon (Ar) gas at different pressures. Nd: YAG laser at various fluences ranging from 7 to 28 J/cm2 was employed to generate Mg plasma. Confinement effects offered by metallic blocker are investigated by placing the blocker at different distances of 6, 8, and 10 mm from the target surface; whereas spatial confinement offered by environmental gas is explored under four different pressures of 5, 10, 20, and 50 Torr. Laser-induced breakdown spectroscopy analysis revealed that both plasma parameters, that is, excitation temperature and electron number density initially are strongly dependent upon both pressures of environmental gases and distances of blockers. The maximum electron temperature of Mg plasma is achieved at Ar gas pressure of 20 Torr, whereas maximum electron number density is achieved at 50 Torr. It is also observed that spatial confinement offered by metallic blocker is responsible for the significant enhancement of both electron temperature and electron number density of Mg plasma. Maximum values of electron temperature and electron number density without blocker are 8335 K and 2.4 × 1016 cm−3, respectively, whereas these values are enhanced to 12,200 K and 4 × 1016 cm−3 in the presence of blocker. Physical mechanisms responsible for the enhancement of Mg plasma parameters are plasma compression, confinement and pronounced collisional excitations due to reflection of shock waves. Scanning electron microscope analysis was performed to explore the surface morphology of laser-ablated Mg. It reveals the formation of ripples and channels that become more distinct in the presence of blocker due to plasma confinement. The optimum combination of blocker distance, fluence and Ar pressure can identify the suitable conditions for defining the role of plasma parameters for surface structuring.
Paratuberculosis is a chronic disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). It occurs worldwide and causes a significant loss in the animal production industry. There is no cure for MAP infection and vaccination is problematic. Identification of genetics of susceptibility could be a useful adjunct for programs that focus on management, testing and culling of diseased animals. A case-control, genome-wide association study (GWAS) was conducted using Holstein and Jersey cattle in a combined analysis in order to identify markers and chromosomal regions associated with susceptibility to MAP infection across-breed. A mixed-model method (GRAMMAR-GC) implemented in the GenABEL R package and a Bayes C analysis implemented in GenSel software were used as alternative approaches to conduct GWAS analysis focused on single SNPs and chromosomal segments, respectively. After conducting quality control, 22 406 SNPs from 2157 individuals were available for the GRAMMAR-GC (Bayes C) analysis and 45 640 SNPs from 2199 individuals were available for the Bayes C analysis. One SNP located on BTA27 (8·6 Mb) was identified as moderately associated (P < 5 × 10−5, FDR = 0·44) in the GRAMMAR-GC analysis of the combined breed data. Nine 1 Mb windows located on BTA 2, 3 (3 windows), 6, 8, 25, 27 and 29 each explained ≥1% of the total proportion of genetic variance in the Bayes C analysis. In an analysis ignoring differences in linkage phase, two moderately significantly associated SNPs were identified; ARS-BFGL-NGS-19381 on BTA23 (32 Mb) and Hapmap40994-BTA-46361 on BTA19 (61 Mb). New common genomic regions and candidate genes have been identified from the across-breed analysis that might be involved in the immune response and susceptibility to MAP infection.
Urinary tract infection (UTI) is common in children aged <5 years with diarrhoea, but little is known about risk factors, aetiology and outcome of such children. We aimed to evaluate these knowledge gaps of UTI in children aged <5 years with diarrhoea. We enrolled all children aged <5 years with diarrhoea admitted to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between May 2011 and April 2013, who had history of fever (⩾38 °C) and obtained a urine sample for culture. Diarrhoea with UTI (confirmed by culture) constituted cases (n = 26) and those without UTI constituted controls (n = 78). Threefold controls were randomly selected. The case-fatality rate was comparable in cases and controls (4% vs. 1%, P = 0·439). Escherichia coli (69%) and Klebsiella (15%) were the most commonly isolated pathogens. Persistent diarrhoea, pneumonia and prior antibiotics use were identified as risk factors for UTI in logistic regression analysis (P < 0·05 for all). Thus, children with diarrhoea presenting with persistent diarrhoea, pneumonia, and prior antibiotic use should be investigated for UTI for their prompt management that may reduce morbidity.
This study aimed to document the growth and challenges encountered in the decade since inception of the National Ambulance Service (NAS) in Ghana, West Africa. By doing so, potentially instructive examples for other low- and middle-income countries (LMICs) planning a formal prehospital care system or attempting to identify ways to improve existing emergency services could be identified.
Data routinely collected by the Ghana NAS from 2004-2014 were described, including: patient demographics, reason for the call, response location, target destination, and ti1mes of service. Additionally, the organizational structure and challenges encountered during the development and maturation of the NAS were reported.
In 2004, the NAS piloted operations with 69 newly trained emergency medical technicians (EMTs), nine ambulances, and seven stations. The NAS expanded service delivery with 199 ambulances at 128 stations operated by 1,651 EMTs and 47 administrative and maintenance staff in 2014. In 2004, nine percent of the country was covered by NAS services; in 2014, 81% of Ghana was covered. Health care transfers and roadside responses comprised the majority of services (43%-80% and 10%-57% by year, respectively). Increased mean response time, stable case holding time, and shorter vehicle engaged time reflect greater response ranges due to increased service uptake and improved efficiency of ambulance usage. Specific internal and external challenges with regard to NAS operations also were described.
The steady growth of the NAS is evidence of the need for Emergency Medical Services and the effects of sound planning and timely responses to changes in program indicators. The way forward includes further capacity building to increase the number of scene responses, strengthening ties with local health facilities to ensure timely emergency medical care and appropriateness of transfers, assuring a more stable funding stream, and improving public awareness of NAS services.
ZakariahA, StewartBT, BoatengE, AchenaC, TansleyG, MockC. The Birth and Growth of the National Ambulance Service in Ghana. Prehosp Disaster Med. 2017;32(1):83–93.
We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6–24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23–25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4–2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0–1·5) times higher risk of URI and 1·9 (95% CI 1·4–2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.
Malaysia introduced graphic health warning labels (GHWLs) on all tobacco packages in 2009. We aimed to examine if implementing GHWLs led to stronger warning reactions (e.g., thinking about the health risks of smoking) and an increase in subsequent quitting activities; and to examine how reactions changed over time since the implementation of the GHWLs in Malaysia and Thailand where GHWL size increased from 50–55% in 2010. Data came from six waves (2005–2014) of the International Tobacco Control Southeast Asia Survey. Between 3,706 and 4,422 smokers were interviewed across these two countries at each survey wave. Measures included salience of warnings, cognitive responses (i.e., thinking about the health risks and being more likely to quit smoking), forgoing cigarettes, and avoiding warnings. The main outcome was subsequent quit attempts. Following the implementation of GHWLs in Malaysia, reactions increased, in some cases to levels similar to the larger Thai warnings, but declined over time. In Thailand, reactions increased following implementation, with no decline for several years, and no clear effect of the small increase in warning size. Reactions, mainly cognitive responses, were consistently predictive of quit attempts in Thailand, but this was only consistently so in Malaysia after the change to GHWLs. In conclusion, GHWLs are responded to more frequently, and generate more quit attempts, but warning wear-out is not consistent in these two countries, perhaps due to differences in other tobacco control efforts.