The Nicaraguan Pediatric Dengue Cohort Study: Incidence of Inapparent and Symptomatic Dengue Virus Infections, 2004–2010

Dengue, caused by the four serotypes of dengue virus (DENV), is the most prevalent mosquito-borne viral disease of humans. To examine the incidence and transmission of dengue, the authors performed a prospective community-based cohort study in 5,545 children aged 2–14 years in Managua, Nicaragua, between 2004 and 2010. Children were provided with medical care through study physicians who systematically recorded medical consult data, and yearly blood samples were collected to evaluate DENV infection incidence. The incidence of dengue cases observed was 16.1 cases (range 3.4–43.5) per 1,000 person-years (95% CI: 14.5, 17.8), and a pattern of high dengue case incidence every other year was observed. The incidence of DENV infections was 90.2 infections (range 45.2–105.3) per 1,000 person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young children (<6 years old) were primary (60%) and the majority of infections in older children (≥9 years of age) were secondary (82%), as expected. The incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI: 102.7, 143.4) was significantly higher than the incidence rate of primary DENV infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous analytic methodology used in this study, including incidence reporting in person-years, allows comparison across studies and across different infectious diseases. This study provides important information for understanding dengue epidemiology and informing dengue vaccine policy.     

Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia

BackgroundDengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia.MethodsOver six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus.ResultsLaboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14–6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77–7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04–1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72–6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33–9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29–0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24–0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients’ serum.ConclusionsAcute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.     

Short-term,medium-term,and long-term risks of nonvariceal upper gastrointestinal bleeding after dengue virus infection

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31–365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51–64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17–95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05–6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89–3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.     

A Meta-Analysis of the Diagnostic Accuracy of Two Commercial NS1 Antigen ELISA Tests for Early Dengue Virus Detection

Background

Dengue virus (DENV) NS1 antigen detection is regarded as an early diagnostic marker. Accordingly, several studies have evaluated the performance of tests that utilize NS1 capture, but the results of individual studies may be limited due to the restricted sample size of the patients recruited. Therefore, our objective was to perform a meta-analysis of the diagnostic accuracy of two commercial NS1 ELISAs (Panbio and Platelia).

Methods and Results

Studies of interest were found in PubMed, Embase and Google Scholar databases using defined inclusion/exclusion criteria. A total of 30 studies containing 12,105 total enrolled patients were included. The results were as follows: 1) Panbio assays showed low overall performance, sensitivity 66% (95% confidence interval (CI) 61–71), specificity 99% (95% CI 96–100), positive likelihood ratio (LR+) 98 (95% CI 20–464), negative likelihood ratio (LR-) 0.3 (95% CI 0.2–0.4), diagnostic odds ratio (DOR) 289 (95% CI 59–1412); 2) Platelia assays showed high overall performance, sensitivity 74% (95% CI 63–82), specificity 99% (95% CI 97–100), LR+ 175 (95% CI 28–1099), LR- 0.3 (95% CI 0.2–0.4), DOR 663 (95% CI 98–4478). The lowest sensitivity values were for secondary infections (57% [95% CI 47–67] and 66% [95% CI 53–77] for Panbio and Platelia, respectively) and for the detection of DENV4. Regarding clinical manifestations, the sensitivity of Platelia was 69% (95% CI 43–86) and 60% (95% CI 48–70) for fever and dengue hemorrhagic fever, respectively. In addition, the sensitivity of both tests was slightly lower for samples from Southeast Asia and Oceania.

Conclusion

DENV1 samples gave higher sensitivity results for both tests. We observed that factors negatively influencing the tests, such as the type of infection, geographical origins of samples and viral serotypes, require further investigation to optimize the diagnostic accuracy.     

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru

Background

Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region.

Methodology/Principal Findings

We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010–2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%–65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1–17.7).

Conclusions/Significance

Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.     

A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese Adults

Background

There is currently no licensed antiviral drug for treatment of dengue. Chloroquine (CQ) inhibits the replication of dengue virus (DENV) in vitro.

Methods and Findings

A double-blind, randomized, placebo-controlled trial of CQ in 307 adults hospitalized for suspected DENV infection was conducted at the Hospital for Tropical Diseases (Ho Chi Minh City, Vietnam) between May 2007 and July 2008. Patients with illness histories of 72 hours or less were randomized to a 3-day course of CQ (n = 153) or placebo (n = 154). Laboratory-confirmation of DENV infection was made in 257 (84%) patients. The primary endpoints were time to resolution of DENV viraemia and time to resolution of DENV NS1 antigenaemia. In patients treated with CQ there was a trend toward a longer duration of DENV viraemia (hazard ratio (HR) = 0.80, 95% CI 0.62–1.05), but we did not find any difference for the time to resolution of NS1 antigenaemia (HR = 1.07, 95% CI 0.76–1.51). Interestingly, CQ was associated with a significant reduction in fever clearance time in the intention-to-treat population (HR = 1.37, 95% CI 1.08–1.74) but not in the per-protocol population. There was also a trend towards a lower incidence of dengue hemorrhagic fever (odds ratio = 0.60, PP 95% CI 0.34–1.04) in patients treated with CQ. Differences in levels of T cell activation or pro- or anti-inflammatory plasma cytokine concentrations between CQ- and placebo-treated patients did not explain the trend towards less dengue hemorrhagic fever in the CQ arm. CQ was associated with significantly more adverse events, primarily vomiting.

Conclusions

CQ does not reduce the durations of viraemia and NS1 antigenaemia in dengue patients. Further trials, with appropriate endpoints, would be required to determine if CQ treatment has any clinical benefit in dengue.

Trial Registration

Current Controlled Trials number ISRCTN38002730.     

Head-to-Head Comparison of Sirolimus-Eluting Stents versus Paclitaxel-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of 76 Studies

Background

The relative short-, long- and overall-term efficacy and safety of sirolimus-eluting stents (SES, Cypher) compared with paclitaxel-eluting stents (PES, Taxus) in large head-to-head comparisons still remain to be defined.

Methods

We searched Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles comparing outcomes of interest between SES and PES without language restriction. Short- (≤1 year), long- (>1 year), and overall-term (the longest follow-up of each study) outcomes were evaluated. The primary endpoint was target lesion revascularization (TLR). Other outcomes of interest were target vessel revascularization (TVR), myocardial infarction, all-cause death, cardiac death, stent thrombosis, major adverse cardiac events (MACEs), restenosis and late lumen loss.

Results

Seventy-six studies including more than 15000 patients in randomized controlled trials and over 70000 patients in adjusted observational studies were included. At overall-term follow-up, SES significantly reduced TLR (relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.49–0.76), TVR (RR: 0.67; 95% CI: 0.54–0.83), MACE (RR: 0.79; 95% CI: 0.72–0.87), myocardial infarction (RR: 0.85; 95% CI: 0.73–0.99), in-segment restenosis (RR: 0.50; 95% CI: 0.38–0.65), and in-segment late lumen loss (weighted mean difference [WMD]: −0.19; 95% CI: −0.24–−0.14) in randomized controlled trials compared with PES. In addition, lower rates of death (RR: 0.91; 95% CI: 0.83–1.00), any stent thrombosis (RR: 0.62; 95% CI: 0.45–0.86), definite stent thrombosis (RR: 0.59; 95% CI: 0.45–0.77) were found in patients receiving SES in adjusted observational studies. Largely similar results were found at short- and long-term follow-up, and in patients with diabetes, acute myocardial infarction or long lesions.

Conclusions

SES significantly reduced the short-, long- and overall-term risk of TLR/TVR, MACE, and restenosis, and overall-term risk of myocardial infarction in randomized controlled trials, as compared with PES. Lower rates of death and stent thrombosis were also observed in observational studies in SES-treated patients.     

Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

Objective

To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors.

Methods

We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates.

Results

The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups.

Conclusions

AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities.     

Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

Objective

Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).

Methods

Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.

Results

In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, p = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, p = 0.28).

Conclusion

Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.     

Comparing the Clinical Outcomes between Drug Eluting Stents and Bare Metal Stents in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials

BackgroundSeveral studies have shown Drug Eluting Stents (DES) to be better compared to Bare Metal Stents (BMS) in patients with type 2 Diabetes Mellitus (T2DM). Since, the adverse clinical outcomes in patients with Insulin-Treated Type 2 Diabetes Mellitus (ITDM) implanted with DES and BMS have not been previously studied, we aim to compare the clinical outcomes in similar patients with cardiovascular diseases, treated with DES and BMS.MethodsRandomized Controlled Trials (RCTs) comparing patients treated with DES and BMS were searched from PubMed and EMBASE databases. Outcome data for the patients with ITDM were carefully extracted. Major Adverse Cardiac Events (MACEs), mortality, Target Vessel Revascularization (TVR), Target Lesion Revascularization (TLR), Myocardial Infarction (MI) and Stent Thrombosis (ST) were considered as the clinical endpoints for this analysis. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software.ResultsTen RCTs consisting of 830 patients with ITDM (477 patients in the DES group and 353 patients in the BMS group) from a total number of 9,141 patients were included in this analysis. During a follow-up period from one month to one year, MACEs were not increased with the use of DES in these patients with ITDM. At 9 months, MACEs were significantly lower in the DES group with OR: 0.40, 95% CI: 0.23–0.72; P = 0.002 with no increase in mortality. TVR and TLR also favored the DES group with OR: 0.44, 95% CI: 0.22–0.88, P = 0.02 and OR: 0.28, 95% CI: 0.14–0.53; P = 0.0001 respectively at 9 months, and OR: 0.46, 95% CI: 0.23–0.94, P = 0.03 and OR: 0.28, 95% CI: 0.14–0.55; P = 0.0003 respectively at one year. Results for MI, and ST were not statistically significant.ConclusionCompared to BMS, DES were associated with a significantly lower rate of repeated revascularization, without any increase in MACEs or mortality in these patients with ITDM during a follow up period of one year. However, due to the very small population size, further studies with a larger number of randomized patients are required to completely solve this issue.     

Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.

Methodology and Principal Findings

In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18).

Conclusion/Significance

B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.     

Trends in the Use of Guideline-Recommended Medications and In-Hospital Mortality of Patients with Acute Myocardial Infarction in a Chinese Population

ObjectiveCurrent practice guidelines recommend the routine use of several cardiac medications early in the course of acute myocardial infarction (AMI). Our objective was to analyze temporal trends in medication use and in-hospital mortality of AMI patients in a Chinese population.MethodsThis is a retrospective observational study using electronic medical records from the hospital information system (HIS) of 14 Chinese hospitals. We identified 5599 patients with AMI between 2005 and 2011. Factors associated with medication use and in-hospital mortality were explored by using hierarchical logistic regression.ResultsThe use of several guideline-recommended medications all increased during the study period: statins (57.7%–90.1%), clopidogrel (61.8%–92.3%), β-Blockers (45.4%–65.1%), ACEI/ARB (46.7%–58.7%), aspirin (81.9%–92.9%), and the combinations thereof increased from 24.9% to 42.8% (P<0.001 for all). Multivariate analyses showed statistically significant increases in all these medications. The in-hospital mortality decreased from 15.9% to 5.7% from 2005 to 2011 (P<0.001). After multivariate adjustment, admission year was still a significant factor (OR = 0.87, 95% CI 0.79–0.96, P = 0.007), the use of aspirin (OR = 0.64, 95% CI 0.46–0.87), clopidogrel (OR = 0.44, 95% CI 0.31–0.61), ACEI/ARB (OR = 0.73, 95% CI 0.56–0.94) and statins (OR = 0.54, 95% CI 0.40–0.73) were associated with a decrease in in-hospital mortality. Patients with older age, cancer and renal insufficiency had higher in-hospital mortality, while they were generally less likely to receive all these medications.ConclusionUse of guideline-recommended medications early in the course of AMI increased between 2005 and 2011 in a Chinese population. During this same time, there was a decrease in in-hospital mortality.     

Clinical Impact of Rapid Reduction of Low-Density Lipoprotein Cholesterol Level on Long-Term Outcome of Acute Myocardial Infarction in the Statin Era: Subanalysis of the ALPS-AMI Study

Background

The optimal period to achieve target percent reduction of low-density lipoprotein cholesterol (LDL-C) level for secondary prevention of acute myocardial infarction (AMI) is not well established.

Methods

The Assessment of Lipophilic vs. Hydrophilic Statin Therapy in AMI (ALPS-AMI) study enrolled 508 patients (mean age, 66.0± 11.6 years; 80.6% male) who were hospitalized for AMI and underwent percutaneous coronary intervention (PCI). Of these patients, 81 were excluded because of the absence of LDL-C measurements at 4 weeks after randomization. In the remaining 427 patients, the target LDL-C level reduction of ≥30% was achieved and not reached within 4 weeks after randomization in 204 cases (early reduction group) and 223 cases (late reduction group). The groups were formed prospectively and analyzed with regard to the composite end point (major adverse cardiovascular event [MACE]: all-cause death, myocardial infarction, and stroke) and clinical outcomes.

Results

MACE were significantly more frequent in the late reduction group compared to the early reduction group (9.4% vs. 3.4%, P = 0.013). The incidence of cardiac deaths was also significantly higher in the late reduction group (3.1% vs. 0.5%, P = 0.044). On age-adjusted Cox proportional hazards analysis in statin-naïve patients, percent reduction of LDL-C level during the initial 4 weeks (HR, 0.98; 95% CI: 0.97–0.99, P = 0.042) and baseline LDL-C level (HR, 0.98; 95% CI: 0.97–0.99, P = 0.033) predicted adverse events.

Conclusions

Rapid reduction of LDL-C level is strongly associated with favorable outcome in patients with AMI.     

High Rates of Pneumonia in Children under Two Years of Age in a South East Asian Refugee Population

Background

There are an estimated 150 million episodes of childhood pneumonia per year, with 11–20 million hospital admissions and 1.575 million deaths. Refugee children are particularly vulnerable, with poorly defined pneumonia epidemiology.

Methods

We followed a birth cohort of 955 refugee infants, born over a one-year period, until two years of age. Clinical and radiographic pneumonia were diagnosed according to WHO criteria. Detailed characteristics were collected to determine risk factors for clinical, radiological and multiple episodes of pneumonia. Investigations were taken during a pneumonia episode to help determine or to infer an aetiological diagnosis.

Findings

The incidence of clinical pneumonia was 0.73 (95% CI 0.70–0.75) episodes per child year (/CY) and of radiological primary endpoint pneumonia (PEP) was 0.22/CY (95% CI 0.20–0.24). The incidence of pneumonia without severe signs was 0.50/CY (95% CI 0.48–0.53), severe pneumonia 0.15/CY (95% CI 0.13–0.17) and very severe pneumonia 0.06/CY (0.05–0.07). Virus was detected, from a nasopharyngeal aspirate, in 61.3% of episodes. A reduced volume of living space per person (IRR 0.99, 95% CI 0.99–1.0, p = 0.003) and young maternal age (IRR 1.59, 95% CI 1.12–2.27, p = 0.01) were risk factors for developing pneumonia. The risk of a child having >1 episode of pneumonia was increased by having a shorter distance to the next house (IRR 0.86, 95% CI 0.74–1.00, p = 0.04). Infants were at risk of having an episode of PEP if there was a shorter distance from stove to bed (IRR 0.89, 95% CI 0.80–0.99, p = 0.03). Raised CRP and neutrophil values were associated with PEP.

Conclusions

There was a high incidence of pneumonia in young children in this SE Asian refugee population. Viral infections were important, however CXR and non-specific marker findings suggested that bacteria may be involved in up to a third of cases.     

A Household Serosurvey to Estimate the Magnitude of a Dengue Outbreak in Mombasa,Kenya, 2013

Dengue appears to be endemic in Africa with a number of reported outbreaks. In February 2013, several individuals with dengue-like illnesses and negative malaria blood smears were identified in Mombasa, Kenya. Dengue was laboratory confirmed and an investigation was conducted to estimate the magnitude of local transmission including a serologic survey to determine incident dengue virus (DENV) infections. Consenting household members provided serum and were questioned regarding exposures and medical history. RT-PCR was used to identify current DENV infections and IgM anti-DENV ELISA to identify recent infections. Of 1,500 participants from 701 households, 210 (13%) had evidence of current or recent DENV infection. Among those infected, 93 (44%) reported fever in the past month. Most (68, 73%) febrile infected participants were seen by a clinician and all but one of 32 participants who reportedly received a diagnosis were clinically diagnosed as having malaria. Having open windows at night (OR = 2.3; CI: 1.1–4.8), not using daily mosquito repellent (OR = 1.6; CI: 1.0–2.8), and recent travel outside of Kenya (OR = 2.5; CI: 1.1–5.4) were associated with increased risk of DENV infection. This survey provided a robust measure of incident DENV infections in a setting where cases were often unrecognized and misdiagnosed.     

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

Background

Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention.

Methods

We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment.

Results

Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious.

Conclusions

High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome.     

Hospital Readmissions of Patients with Heart Failure: The Impact of Hospital and Primary Care Organizational Factors in Northern Italy

BackgroundPrimary health care is essential for an appropriate management of heart failure (HF), a disease which is a major clinical and public health issue and a leading cause of hospitalization. The aim of this study was to evaluate the impact of different organizational factors on readmissions of patients with HF.MethodsThe study population included elderly resident in the Local Health Authority of Bologna (Northern Italy) and discharged with a diagnosis of HF from January to December 2010. Unplanned hospital readmissions were measured in four timeframes: 30 (short-term), 90 (medium-term), 180 (mid-long-term), and 365 days (long-term). Using multivariable multilevel Poisson regression analyses, we investigated the association between readmissions and organizational factors (discharge from a cardiology department, general practitioners’ monodisciplinary organizational arrangement, and implementation of a specific HF care pathway).ResultsThe 1873 study patients had a median age of 83 years (interquartile range 77–87) and 55.5% were females; 52.0% were readmitted to the hospital for any reason after a year, while 20.1% were readmitted for HF. The presence of a HF care pathway was the only factor significantly associated with a lower risk of readmission for HF in the short-, medium-, mid-long- and long-term period (short-term: IRR [incidence rate ratio]=0.57, 95%CI [confidence interval]=0.35–0.92; medium-term: IRR=0.70, 95%CI=0.51–0.96; mid-long-term: IRR=0.79, 95%CI=0.64–0.98; long-term: IRR=0.82, 95%CI=0.67–0.99), and with a lower risk of all-cause readmission in the short-term period (IRR=0.73, 95%CI=0.57–0.94).ConclusionOur study shows that the HF care specific pathway implemented at the primary care level was associated with lower readmission rate for HF in each timeframe, and also with lower readmission rate for all causes in the short-term period. Our results suggest that the engagement of primary care professionals starting from the early post-discharge period may be relevant in the management of patients with HF.