Metabolic and genetic risk factors associated with pre-diabetes and type 2 diabetes in Thai healthcare employees: A long-term study from the Siriraj Health (SIH) cohort study.

BACKGROUND: The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age population. We aim to assess the prevalence and incidence of risk factors and their associations underlying NCDs, especially type-2 diabetes mellitus (T2DM) among healthcare workers enrolled in the Siriraj Health (SIH) study cohort. METHODS: The SIH study was designed as a longitudinal cohort and conducted at Siriraj hospital, Thailand. A total of 5,011 participants (77% women) were recruited and follow-up. Physical examinations, blood biochemical analyses, family history assessments, behavior evaluations, and genetics factors were assessed. RESULTS: The average age was 35.44±8.24 years and 51% of participants were overweight and obese. We observed that men were more likely to have a prevalence of T2DM and dyslipidemia (DLP) compared to women. Aging was significantly associated with pre-diabetes and T2DM (P<0.001). Additionally, aging, metabolic syndrome, and elevated triglycerides were associated with the development of pre-diabetes and T2DM. The minor T allele of the rs7903146(C/T) and rs4506565 (A/T) were associated with a high risk of developing pre-diabetes with odds ratios of 2.74 (95% confidence interval [CI]: 0.32-23.3) and 2.71 (95% CI: 0.32-23.07), respectively; however, these associations were statistically insignificant (P>0.05). CONCLUSION: The findings of the SIH study provide a comprehensive understanding of the health status, risk factors, and genetic factors related to T2DM in a specific working population and highlight areas for further research and intervention to address the growing burden of T2DM and NCDs.

Protocol-directed vs. physician-directed weaning from ventilator in intra-abdominal surgical patients.

BACKGROUND: Previous studies have demonstrated that protocol-directed weaning is better than physician-directed weaning in terms of shorter duration of mechanical ventilation in general critically ill patients. In this prospective, randomized controlled trial, the authors compared duration of mechanical ventilation between protocol based nurse-directed weaning and physician-directed weaning in patients following intra-abdominal surgery. MATERIAL AND METHOD: One hundred intra-abdominal surgical patients requiring mechanical ventilation for more than 24 hours were randomly assigned to receive either protocol-directed (n=51) or physician-directed (n=49) weaning from mechanical ventilation. Patients assigned to the protocol-directed weaning group underwent daily screening and a spontaneous breathing trial by nursing staff OUTCOMES: The primary outcome was the duration of mechanical ventilation. RESULTS: The median duration of mechanical ventilation was 40 and 72 hrs in protocol-directed and physician-directed groups, respectively (p < 0.001). Two patients in the protocol-directed group and three patients in the physician directed group were re-intubated within the first 72 hours after extubation (p = 0.61). CONCLUSION: Daily screening of respiratory function in intra-abdominal surgical patients followed by trials ofspontaneous breathing performed by nurses resulted in a shorter duration of mechanical ventilation when compared to traditional physician-directed weaning.

Variation in cerebral blood flow velocity with cerebral perfusion pressure >40 mm Hg in 42 children with severe traumatic brain injury.

OBJECTIVE: : To determine the prevalence of low, normal, and high mean middle cerebral artery flow velocity when cerebral perfusion pressure is >40 mm Hg in children with severe traumatic brain injury. There is no information regarding the relationship between middle cerebral artery flow velocity and cerebral perfusion pressure in pediatric traumatic brain injury. DESIGN: : Prospective, observational study. SETTING: : Level I pediatric trauma center. PATIENTS: : A total of 42 children <17 yrs of age with an admission diagnosis of severe traumatic brain injury (admission Glasgow Coma Scale score of <9), traumatic brain injury on computed tomography scan, tracheal intubation/mechanical ventilation, and intracranial pressure monitoring. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Bilateral middle cerebral arteries were insonated using transcranial Doppler ultrasonography to calculate mean middle cerebral artery flow velocity after traumatic brain injury. Low mean middle cerebral artery flow velocity was defined as middle cerebral artery flow velocity <2 standard deviation and high was defined as mean middle cerebral artery flow velocity >2 standard deviation. Patients were grouped by age (0.8-2.9, 3-5.9, 6-9.9, and 10-16.9 yrs) and gender to examine the relationship between cerebral perfusion pressure and low, high, or normal mean middle cerebral artery flow velocity. Potential confounders of the relationship between cerebral perfusion pressure and mean middle cerebral artery flow velocity (intracranial pressure, PaCO2, hematocrit, sedation, fever,and impaired autoregulation were examined). Most children (n = 33; 79%) had normal mean middle cerebral artery flow velocity but four patients (9%) had low mean middle cerebral artery flow velocity and five children (12%) had high mean middle cerebral artery flow velocity despite cerebral perfusion pressure >40 mm Hg. There was no difference in potential confounders of the relationship between cerebral perfusion pressure and mean middle cerebral artery flow velocity except for hematocrit, which was lower (25 +/- 4%; range = 21-30%) in children with high mean middle cerebral artery flow velocity. An inverse relationship between mean middle cerebral artery flow velocity and hematocrit was also found in boys aged 10 to 16.9 yrs. CONCLUSIONS: : Both low and/or high mean middle cerebral artery flow velocity occur with cerebral perfusion pressure >40 mm Hg in severe pediatric traumatic brain injury. Of the potential confounders considered, only lower hematocrit was associated with high mean middle cerebral artery flow velocity.

Cerebrovascular pathophysiology in pediatric traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of traumatic morbidity and mortality in children. Although there is increasing information concerning TBI in adults and experimental animal models, relatively little is known regarding cerebrovascular pathophysiology specific to children. MATERIALS: A review of the pertinent medical literature. RESULTS: Systemic and cerebral hemodynamic factors such as hypotension, hypoxia, hyperglycemia, and fever are associated with poor outcome in pediatric TBI. Similarly, cerebral autoregulation is often impaired after TBI and may adversely affect outcome, especially if systemic hemodynamics are altered. Furthermore, CO2 vasoreactivity may be altered after pediatric TBI and lead to either cerebral ischemia or hyperemia. CONCLUSIONS: Understanding the effect of pediatric TBI on the cerebral circulation is needed to potentially develop protocols to improve outcome in this vulnerable population. Specifically, changes in pediatric cerebrovascular physiology and pathophysiology, including CO2 vasoreactivity and pressure autoregulation, must be understood and their mechanism elucidated.

Cerebral hemodynamic predictors of poor 6-month Glasgow Outcome Score in severe pediatric traumatic brain injury.

Little is known regarding the cerebral autoregulation in pediatric traumatic brain injury (TBI). We examined the relationship between cerebral hemodynamic predictors, including cerebral autoregulation, and long-term outcome after severe pediatric TBI. After Institutional Review Board (IRB) approval, a retrospective analysis of prospectively collected data (May 2002 to October 2007) for children age < or =16 years with severe TBI (admission Glasgow Coma Scale [GCS] score <9) was performed. Cerebral autoregulation was assessed within 72 h after TBI. Cerebral hemodynamic predictors (intracranial pressure [ICP], systolic blood pressure [SBP], and cerebral perfusion pressure [CPP]) through the first 72 h after TBI were abstracted. Univariate and multivariate analyses examined the relationship between impaired cerebral autoregulation (autoregulatory index <0.4), intracranial hypertension (ICP >20 mm Hg), and hypotension (SBP <5th percentile and CPP <40 mm Hg). Six-month Glasgow Outcome Scale (GOS) score of <4 defined poor outcome. Ten (28%) of the 36 children examined (9.1 +/- 5.3 [0.8-16] years; 74% male) had poor outcome. Univariate factors associated with poor outcome were impaired cerebral autoregulation (p = 0.005), SBP <5(th) percentile for age and gender (p = 0.02), and low middle cerebral artery flow velocity (<2 SD for age and gender; p = 0.04). Independent risk factors for poor 6-month GOS were impaired cerebral autoregulation (adjusted odds ratio [aOR] 12.0; 95% confidence interval [CI] 1.4-99.4) and hypotension (SBP <5th percentile; aOR 8.8; 95% CI 1.1-70.5), respectively. Previous studies of TBI describing poor outcome with hemodynamics did not consider the status of cerebral autoregulation. In this study, both impaired cerebral autoregulation and SBP <5th percentile were independent risk factors for poor 6-month GOS.

Cerebral blood flow and autoregulation after pediatric traumatic brain injury.

Traumatic brain injury is a global health concern and is the leading cause of traumatic morbidity and mortality in children. Despite a lower overall mortality than in adult traumatic brain injury, the cost to society from the sequelae of pediatric traumatic brain injury is very high. Predictors of poor outcome after traumatic brain injury include altered systemic and cerebral physiology, including altered cerebral hemodynamics. Cerebral autoregulation is often impaired after traumatic brain injury and may adversely impact the outcome. Although altered cerebrovascular hemodynamics early after traumatic brain injury may contribute to disability in children, there is little information regarding changes in cerebral blood flow and cerebral autoregulation after pediatric traumatic brain injury. This review addresses normal pediatric cerebral physiology and cerebrovascular pathophysiology after pediatric traumatic brain injury.

Young age as a risk factor for impaired cerebral autoregulation after moderate to severe pediatric traumatic brain injury.

BACKGROUND: Little is known about age and cerebral autoregulation in children with traumatic brain injury (TBI). The authors compared cerebral autoregulation between young (aged <4 yr) and older (aged > or =4 yr) children with TBI. METHODS: After University of Washington's institutional review board approval, a retrospective analysis of prospectively collected data (May 2002 and June 2007) was performed. Eligibility criteria included age 16 yr or younger, moderate to severe (admission Glasgow Coma Scale score <13) TBI, TBI on computed tomography scan, and tracheal intubation. Cerebral autoregulation testing was performed within 72 h after TBI, and autoregulation was quantified using the autoregulatory index. An autoregulatory index less than 0.4 represents impaired cerebral autoregulation. The 12-month Glasgow outcome score was measured. Data are presented as mean +/- SD or range. RESULTS: Thirty-seven children (8.9 +/- 5.1 yr; 0.8-16 yr) were enrolled. Children younger than 4 yr had a higher incidence of impaired cerebral autoregulation (8 of 10 vs. 7 of 27; P = 0.006) and worse 12-month outcome (Glasgow outcome score 3.0 +/- 1.0 vs. 4.0 +/- 1.0; P = 0.02) than older children. Age less than 4 yr (adjusted odds ratio, 12.2; 95% confidence interval, 1.5-98.5) and low Glasgow Coma Scale score (adjusted odds ratio for higher Glasgow Coma Scale, 0.53; 95% confidence interval, 0.30-0.96) were independently associated with impaired cerebral autoregulation. CONCLUSIONS: Age less than 4 yr was a risk factor for impaired cerebral autoregulation, independent of TBI severity. Age-related factors may play a role in the mechanisms maintaining or worsening cerebral autoregulation in children after TBI.

Antipyretic treatment of noninfectious fever in children with severe traumatic brain injury.

OBJECTIVE: The purpose of this study was to describe the treatment of noninfectious fever in children with severe traumatic brain injury (TBI). MATERIALS AND METHODS: We conducted a retrospective study to compare type of and response to antipyretic treatment strategies in children less than or equal to 17 years and Glasgow Coma Scale (GCS) score less than 9. RESULTS: The average admission GCS score was 4. Forty children (35 boys, 5 girls), age 7.8 +/- 5.2 years, had noninfectious fever. Seventy percent (28 of 40) received acetaminophen only, and 30% (12 of 40) received acetaminophen plus either ibuprofen or physical cooling. Time to next febrile episode was longer in patients receiving combination therapy than those receiving monotherapy (p = 0.03). Fever refractory to treatment dose or strategy occurred in more than 40% of the patients. CONCLUSIONS: Early combination antipyretic therapy may be needed to effectively maintain normothermia in children with severe TBI.

Hemispheric differences in cerebral autoregulation in children with moderate and severe traumatic brain injury.

INTRODUCTION: To examine hemispheric differences in cerebral autoregulation in children with traumatic brain injury (TBI). After IRB approval and consent, subjects underwent static cerebral autoregulation testing during the first 9 days after PICU admission. Cerebral autoregulation was quantified using the autoregulatory index (ARI). RESULTS: Forty-two (27 M:15 F) children (10 +/- 5 years) with TBI and admission Glasgow coma scale score (5 +/- 2) were enrolled. Seven (54%) of the 13 children with focal TBI and 8 (28%) of 29 children with diffuse TBI had impairment or absence of cerebral autoregulation of at least one hemisphere. In patients with isolated focal TBI, ARI was lower (0.40 +/- 0.40 vs. 0.67 +/- 0.40; P = 0.03) in the side of TBI than in the unaffected hemisphere, but cerebral autoregulation was often impaired on the side without TBI or shift (5/13) on head CT. There was no difference in ARI between hemispheres in children with diffuse TBI, with or without superimposed focal lesions (P = 0.17). Patients with bilateral intact cerebral autoregulation tended to have higher 6 month Glasgow Outcome Score (GOS) than patients with either unilateral or bilateral cerebral autoregulation impairment (GOS 4.0 +/- 0.60 vs. 3.6 +/- 0.80; P = 0.08). CONCLUSIONS: Hemispheric differences in cerebral autoregulation were common in children with isolated focal TBI. Absence of TBI on CT was not always associated with intact cerebral autoregulation. Patients with bilaterally intact cerebral autoregulation tended to have better outcomes.

Change in cerebral autoregulation as a function of time in children after severe traumatic brain injury: a case series.

OBJECTIVE: The objective of this study was to describe changes in cerebral autoregulation after severe pediatric traumatic brain injury (TBI). MATERIALS AND METHODS: Two cerebral autoregulation tests were performed during the first 10 days after severe TBI in children <16 years. Cerebral autoregulation was quantified using the mean autoregulatory index (mARI). RESULTS: Nine (five males/four females) children (10 +/- 5 years) with severe (admission Glasgow Coma Scale (GCS), 5 +/- 2) TBI were enrolled. Thirty (3/9) percent of initial exams revealed impaired cerebral autoregulation; all three had returned to intact cerebral autoregulation on second exam. However, in three of nine (33%) patients, cerebral autoregulation worsened on second exam. Of the factors examined, worsening mARI on second exam was associated with worsening head computed tomography (CT) lesion. CONCLUSIONS: Cerebral autoregulation often changed and worsened during the first 9 days after severe pediatric TBI. Worsening cerebral autoregulation may mirror worsening TBI.