HIV Case Notification Rates in the Kingdom of Saudi Arabia over the Past Decade (2000–2009)

Objective

To study trends in HIV case notification rates in the Kingdom of Saudi Arabia.

Design

A ten year retrospective review of annual HIV case notification returns to the Ministry of Health, Kingdom of Saudi Arabia.

Methods

Annual Registry statistics covering the period 2000 to 2009 were reviewed. Annual incidence trends were stratified according to the following demographics: age, nationality, geographical region of residence, gender, and mode of disease acquisition.

Results

10,217 new HIV cases (2,956 in Saudi nationals and 7,261 in non-Saudis) were reported. Africans of Sub-Saharan Africa origin accounting for 3,982/7,261 (53%) of non-Saudi cases constituted: Ethiopians (2,271), Nigerians (1,048), and Sudanese nationals (663). The overall average annual incidence was <4 cases per 100,000; 1.5 cases per 100,000 for Saudis (range 0.5–2.5), and 13.2 per 100,000 for non-Saudis (range 5.7–19.0). Notifications increased yearly from 2000 for both groups until a plateau was reached in 2006 at 1,390 new cases. Case notification in Saudi nationals increased from 20% in the early 2001 to 40% in 2009. 4% (124/2,956) of cases were reported in Saudi children. The male to female ratio was 1.6∶1 for non-Saudi nationals (43.8% male, 27.3% female) and 4.4∶1 for Saudis (23.5% male, 5.4% female).

Conclusions

Whilst the numbers of reported HIV cases have stabilised since 2006, HIV/AIDS remains an important public health problem in KSA, both in migrants and Saudi nationals. HIV transmission to Saudi children is also of concern. Optimization of data collection, surveillance, and pro-active screening for HIV is required.     

Predicting Outcome on Admission and Post-Admission for Acetaminophen-Induced Acute Liver Failure Using Classification and Regression Tree Models

Background/Aim

Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF) patients often presents significant challenges. King’s College (KCC) has been validated on hospital admission, but little has been published on later phases of illness. We aimed to improve determinations of prognosis both at the time of and following admission for APAP-ALF using Classification and Regression Tree (CART) models.

Methods

CART models were applied to US ALFSG registry data to predict 21-day death or liver transplant early (on admission) and post-admission (days 3-7) for 803 APAP-ALF patients enrolled 01/1998–09/2013. Accuracy in prediction of outcome (AC), sensitivity (SN), specificity (SP), and area under receiver-operating curve (AUROC) were compared between 3 models: KCC (INR, creatinine, coma grade, pH), CART analysis using only KCC variables (KCC-CART) and a CART model using new variables (NEW-CART).

Results

Traditional KCC yielded 69% AC, 90% SP, 27% SN, and 0.58 AUROC on admission, with similar performance post-admission. KCC-CART at admission offered predictive 66% AC, 65% SP, 67% SN, and 0.74 AUROC. Post-admission, KCC-CART had predictive 82% AC, 86% SP, 46% SN and 0.81 AUROC. NEW-CART models using MELD (Model for end stage liver disease), lactate and mechanical ventilation on admission yielded predictive 72% AC, 71% SP, 77% SN and AUROC 0.79. For later stages, NEW-CART (MELD, lactate, coma grade) offered predictive AC 86%, SP 91%, SN 46%, AUROC 0.73.

Conclusion

CARTs offer simple prognostic models for APAP-ALF patients, which have higher AUROC and SN than KCC, with similar AC and negligibly worse SP. Admission and post-admission predictions were developed.

Key Points

• Prognostication in acetaminophen-induced acute liver failure (APAP-ALF) is challenging beyond admission• Little has been published regarding the use of King’s College Criteria (KCC) beyond admission and KCC has shown limited sensitivity in subsequent studies• Classification and Regression Tree (CART) methodology allows the development of predictive models using binary splits and offers an intuitive method for predicting outcome, using processes familiar to clinicians• Data from the ALFSG registry suggested that CART prognosis models for the APAP population offer improved sensitivity and model performance over traditional regression-based KCC, while maintaining similar accuracy and negligibly worse specificity• KCC-CART models offered modest improvement over traditional KCC, with NEW-CART models performing better than KCC-CART particularly at late time points     

Knowledge,Attitudes and Perceptions of Saudis towards Participating in Clinical Trials

Aim

To assess the knowledge, attitudes, and perceptions of Saudis towards participating in clinical trials (CTs).

Methods

A cross-sectional study was conducted on 232 Saudi adult patients and their companions visiting adult outpatient clinics at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected using a self-administered questionnaire based on information obtained from the literature. The questionnaire was divided into four sections, one covering the respondents’ demographics, and the other three assessing knowledge, attitudes, and perceptions towards participating in CTs.

Results

A total of 148 (63.8%) respondents were males, and 52 (22.4%) participants had been invited to participate in a CT previously. Of those, 39 (75%) participated. Knowledge about the essential elements of informed consent ranged from 55.7% (number of participants needed) to 85.7% (confidentiality of personal information). The majority (163, 73.8%) of respondents was willing to participate in a CT after consulting their family physician and 130 (58.0%) respondents would be motivated to participate in a CT if they were healthy. Only 36.8% of the respondents believed that patients who participated in a CT received the best care. Moreover, 110 (48.7%) respondents believed that research was conducted in a responsible and ethical manner.

Conclusions

The present study assessed the current understanding of CTs among Saudi participants. Although the majority of participants had an acceptable level of knowledge about CTs, they exhibited conditional attitudes and misperceptions towards participating in a CT. Increased patient awareness may improve patients’ attitudes towards ethical conduct of CTs.     

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

Background

Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased.

Methods

We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods.

Results

A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis.

Conclusions

In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data.     

Nutritional Status and Nosocomial Infections among Adult Elective Surgery Patients in a Mexican Tertiary Care Hospital

Background

Controversy exists as to whether obesity constitutes a risk-factor or a protective-factor for the development of nosocomial Infection (NI). According to the obesity-paradox, there is evidence that moderate obesity is a protective-factor. In Mexico few studies have focused on the nutritional status (NS) distribution in the hospital setting.

Objectives

The aim of this study was to estimate the distribution of NS and the prevalence of nosocomial infection NI among adult elective surgery (ES) patients and to compare the clinical and anthropometric characteristics and length of stays (LOS) between obese and non-obese patients and between patients with and without NI.

Methods

We conducted a cross-sectional study with a sample (n = 82) adult ES patients (21–59 years old) who were recruited from a tertiary-care hospital. The prevalences of each NS category and NI were estimated, the assessments were compared between groups (Mann-Whitney, Chi-squared or the Fisher''s-exact-test), and the association between preoperative risk-factors and NI was evaluated using odds ratios.

Results

The distribution of subjects by NS category was: underweight (3.66%), normal-weight (28.05%), overweight (35.36%), and obese (32.93%). The prevalence of NI was 14.63%. The LOS was longer (p<0.001) for the patients who developed NI. The percentages of NI were: 33.3% in underweight, 18.52% in obese, 17.39% in normal-weight, and 6.90% in overweight patients.

Conclusion

The prevalence of overweight and obesity in adult ES patients is high. The highest prevalence of NI occurred in the underweight and obese patients. The presence of NI considerably increased the LOS, resulting in higher medical care costs.     

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study

Objective

To investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment.

Methods

By using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months.

Results

A total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group.

Conclusion

In “real-world” diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug—drug interaction.     

Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study

Background

Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.

Methods

118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.

Results

By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.

Conclusions

Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.     

The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

Aims

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS).

Methods

Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor.

Results

The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs.

Conclusion

The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.     

Breast Cancer Screening in Saudi Arabia: Free but Almost No Takers

Introduction

Mammography ensures early diagnosis and a better chance for treatment and recovery from breast cancer. We conducted a national survey to investigate knowledge and practices of breast cancer screening among Saudi women aged 50 years or older in order to inform the breast cancer national health programs.

Materials and Methods

The Saudi Health Interview Survey is a national multistage survey of individuals aged 15 years or older. The survey included questions on socio-demographic characteristics, tobacco consumption, diet, physical activity, health-care utilization, different health-related behaviors, and self-reported chronic conditions. Female respondents were asked about knowledge and practices of self and clinical breast exams, as well as mammography.

Results

Between April and June 2013, a total of 10,735 participants completed the survey. Among respondents, 1,135 were women aged 50 years or older and were included in this analysis. About 89% of women reported not having a clinical breast exam in the past year, and 92% reported never having a mammogram. Women living in Al Sharqia had the highest rate of mammography use. Women who were educated, those who had received a routine medical exam within the last two years, and those who were diagnosed with hypertension were more likely to have had a mammogram in the past two years.

Discussion

Our results show very low rates of breast cancer screening in the Kingdom of Saudi Arabia, a country with free health services. This calls for educational campaigns to improve breast cancer screening. Addressing the barriers for breast cancer screening is a public health imperative.     

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Background

Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.

Objectives

To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).

Patients

Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.

Results

At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.

Conclusions

Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.

Trial Registration

ClinicalTrials.gov NCT01339026     

Butyrylcholinesterase Predicts Cardiac Mortality in Young Patients with Acute Coronary Syndrome

Background

The incidence of acute coronary syndrome (ACS) in young people (≤65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE).

Methods

Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to “young patients” (45–64 years), "middle-aged patients” (65–84 years) and “old patients” (85–100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival.

Results

After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0–6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53–0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45–64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12–0.64, p = 0.003), a weaker association with mortality in middle aged (65–84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41–1.06], p = 0.087), and no association in older patients (85–100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58–1.38], p = 0.613).

Conclusion

BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes.     

Angiographic Lesion Complexity Score and In-Hospital Outcomes after Percutaneous Coronary Intervention

Objective

We devised a percutaneous coronary intervention (PCI) scoring system based on angiographic lesion complexity and assessed its association with in-hospital complications.

Background

Although PCI is finding increasing application in patients with coronary artery disease, lesion complexity can lead to in-hospital complications.

Methods

Data from 3692 PCI patients were scored based on lesion complexity, defined by bifurcation, chronic total occlusion, type C, and left main lesion, along with acute thrombus in the presence of ST-segment elevation myocardial infarction (1 point assigned for each variable).

Results

The patients’ mean age was 67.5 +/- 10.8 years; 79.8% were male. About half of the patients (50.3%) presented with an acute coronary syndrome, and 2218 (60.1%) underwent PCI for at least one complex lesion. The patients in the higher-risk score groups were older (p < 0.001) and had present or previous heart failure (p = 0.02 and p = 0.01, respectively). Higher-risk score groups had significantly higher in-hospital event rates for death, heart failure, and cardiogenic shock (from 0 to 4 risk score; 1.7%, 4.5%, 6.3%, 7.1%, 40%, p < 0.001); bleeding with a hemoglobin decrease of >3.0 g/dL (3.1%, 11.0%, 13.1%, 10.3%, 28.6%, p < 0.001); and postoperative myocardial infarction (1.5%, 3.1%, 3.8%, 3.8%, 10%, p = 0.004), respectively. The association with adverse outcomes persisted after adjustment for known clinical predictors (odds ratio 1.72, p < 0.001).

Conclusion

The complexity score was cumulatively associated with in-hospital mortality and complication rate and could be used for event prediction in PCI patients.     

Impact of Coronary Dominance on In-Hospital Outcomes after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome

Objective

This study evaluated the manner in which coronary dominance affects in-hospital outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Background

Previous studies have shown that left dominant coronary anatomies are associated with worse prognoses in patients with coronary artery disease.

Methods

Data were analyzed from 4873 ACS patients undergoing PCI between September 2008 and April 2013 at 14 hospitals participating in the Japanese Cardiovascular Database Registry. The patients were grouped based on diagnostic coronary angiograms performed prior to PCI; those with right- or co-dominant anatomy (RD group) and those with left-dominant anatomy (LD group).

Results

The average patient age was 67.6±11.8 years and both patient groups had similar ages, coronary risk factors, comorbidities, and prior histories. The numbers of patients presenting with symptoms of heart failure, cardiogenic shock, or cardiopulmonary arrest were significantly higher in the LD group than in the RD group (heart failure: 650 RD patients [14.7%] vs. 87 LD patients [18.8%], P = 0.025; cardiogenic shock: 322 RD patients [7.3%] vs. 48 LD patients [10.3%], P = 0.021; and cardiopulmonary arrest: 197 RD patients [4.5%] vs. 36 LD patients [7.8%], P = 0.003). In-hospital mortality was significantly higher among LD patients than among RD patients (182 RD patients [4.1%] vs. 36 LD patients [7.8%], P = 0.001). Multivariate logistic regression analysis revealed that LD anatomy was an independent predictor for in-hospital mortality (odds ratio, 1.75; 95% confidence interval, 1.06–2.89; P = 0.030).

Conclusion

Among ACS patients who underwent PCI, LD patients had significantly worse in-hospital outcomes compared with RD patients, and LD anatomy was an independent predictor of in-hospital mortality.     

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

Background

Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.

Methods

A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.

Results

Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.

Conclusions

The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01335087","term_id":"NCT01335087"}}NCT01335087     

Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of Women at Risk of Imminent Preterm Birth: A Systematic Review and Meta-Analysis

Background

This study synthesizes available evidence on antenatal corticosteroids (ACS) use among special subgroups of women at risk of imminent preterm birth, including those (1) with pregestational and gestational diabetes mellitus, (2) undergoing elective caesarean section (CS) in late preterm (34 to<37 weeks), (3) with chorioamnionitis, and (4) with growth-restricted fetuses.

Methods

A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, POPLINE, and World Health Organization Regional Databases was conducted for all comparative studies. Two reviewers independently determined study eligibility, extracted data, and assessed study quality. Pooled mean differences and odds ratios with 95% confidence intervals were estimated from available data, based on fixed- and random-effects models, as appropriate.

Results

No eligible studies were identified for ACS use in diabetic pregnant women or those undergoing elective CS at late preterm. Nine studies each on ACS use in women with chorioamnionitis and in women with fetal growth restriction met inclusion criteria; eight studies were separately included in the meta-analyses for the two subpopulations. For ACS administration in women with chorioamnionitis, pooled analyses showed reductions in neonatal mortality (OR: 0.49, 95% CI: 0.34–0.73), respiratory distress syndrome (OR: 0.58, 95% CI: 0.44–0.76), intraventricular haemorrhage (OR: 0.41, 95% CI: 0.24–0.69), and severe intraventricular haemorrhage (OR: 0.40, 95% CI: 0.24–0.69). Maternal and long-term newborn outcomes were not reported. Effects of ACS use were inconclusive for cases with fetal growth restriction.

Conclusion

Direct evidence on the effectiveness and safety of ACS is lacking for diabetic pregnant women at risk of preterm birth and those undergoing elective late-preterm CS, though this does not necessarily recommend against their use in diabetic women. While evidence remains inconclusive for women with growth-restricted preterm neonates, ACS appears to benefit preterm neonates delivered by women with chorioamnionitis. High-quality studies on maternal and long-term child outcomes in more diverse settings are needed to establish the balance of potential harms versus benefits in using ACS for these understudied subgroups.     

Genome-Wide Association Study Identifies That the ABO Blood Group System Influences Interleukin-10 Levels and the Risk of Clinical Events in Patients with Acute Coronary Syndrome

Introduction

Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients.

Method

We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers.

Results

Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 × 10⁻¹⁰) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 × 10⁻¹³), and soluble tissue factor (sTF, P = 8.6 × 10⁻⁴) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 × 10⁻¹⁵ and P = 1.0 × 10⁻⁵ respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24–1.29, P = 0.029–0.00067).

Conclusion

Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease.     

The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis

Objective

Few data are available on the role of T lymphocytes and inflammatory cytokines in abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP). We conducted a retrospective study to assess the risk factors associated with ACS in SAP.

Methods

A total of 76 SAP patients who were admitted within 24 hours after symptom onset in our study. There were 36 patients suffering from ACS and 40 from intra-abdominal hypertension (IAH). On the 1^st, 3^rd and 7^th days after hospital admission, the following variables were assessed: serum value of C-reactive protein (CRP), and the proportions of peripheral CD4⁺ and CD8⁺ T lymphocytes. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and computed tomography severity index (CTSI) score were assessed on days 1 and 7 after hospitalization.

Results

Compared with the patients with IAH, ACS patients showed statistically higher CRP value on 7^th day after hospital admission, proportions of CD4⁺ T cells on days 1, 3, 7 and CD4⁺ / CD8⁺ ratio on day 1 were significantly lower (P < 0.05, respectively). A CD4⁺ T cell proportion of 30.3% on the 1^st day indicated ACS with an area under the curve (AUC) of 0.774, a sensitivity with 82.5% and specificity with 72.0%, respectively. Sensitivity / specificity for predicting ACS in SAP patients on day 1 was 70.0% / 68.0% for CD4⁺ / CD8⁺ ratio, 72.2% / 65.0% for APACHE II score.

Conclusions

The reduction of peripheral blood CD4⁺ T lymphocytes is associated with ACS in SAP, and may act as a potential predictor of ACS in SAP.     

Sensitivity and Specificity of a Novel Classifier for the Early Diagnosis of Dengue

Background

Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020.

Methods

5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases.

Results

The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%).

Conclusions

We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies.