Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis

Context

Gastroenteritis remains a leading cause of childhood morbidity.

Objective

Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected.

Data Sources

MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings.

Study Selection

Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate.

Data Extraction

The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models.

Results

31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92).

Conclusions

There is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be used. Routine probiotic use cannot be endorsed at this time in outpatient children with gastroenteritis. Despite some evidence that ondansetron administration increases diarrhea frequency, emergency department use leads to reductions in intravenous rehydration and hospitalization. No benefits were associated with ondansetron use following emergency department discharge.     

Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy

Objectives

To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients.

Methods

Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals.

Results

Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years.

Conclusion

TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.     

Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS)

Objectives

We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study.

Methods

Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression.

Results

Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5–4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83–1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78–3.09), female IDU (2.33, 1.59–3.39) and white heterosexual men (1.32, 0.94–1.84) compared to white heterosexual women and homosexual men (0.53, 0.29–0.95; and 0.71, 0.55–0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94–1.45 vs. 0.86, 0.71–1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10–0.31; vs. 0.04, 0.02–0.10; P = 0.003).

Conclusions

Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care.     

Effective Linkages of Continuum of Care for Improving Neonatal,Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis

Background

Continuum of care has the potential to improve maternal, newborn, and child health (MNCH) by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood) and space dimensions (from community-family care to clinical care). However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries.

Methods

We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers’ uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality.

Results

Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I² 79%). Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I² 81%).

Conclusions

Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the reduction of neonatal and perinatal deaths. Although maternal deaths were not significantly reduced, composite measures of all mortality were. Thus, the evidence is sufficient to scale up this intervention package for the improvement of MNCH outcomes.     

Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study

Background

In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV) and virological failure (VF) under combined antiretroviral therapy (cART).

Materials and Methods

We analysed patients receiving standard regimens between 1^st July 2012 and 1^st July 2013 with at least one viral load (VL) measurement below the quantification limit (BLQ) in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models.

Results

Of 2276 participants, 1972 (86.6%) were BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI): 4.19 (2.07–8.49); for 10.000–99.999 copies/mL: aOR (95% CI): 2.52 (1.23–5.19)] and shorter cART duration [for <9 months: aOR (95% CI): 2.59 (1.38–4.86)]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI): 2.76 (1.03–7.35); for 30–50 years: aOR (95% CI): 2.70 (1.26–5.79)], people originating from high prevalence countries [aOR (95% CI): 2.20 (1.09–4.42)] and in male injecting drug users [aOR (95% CI): 2.72 (1.38–5.34)].

Conclusions

For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.     

Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

Background

With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).

Methods

We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points.

Results

Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14).

Conclusion

Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.     

Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10^-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated.     

Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

Objective

It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design

Observational, epidemiological study design.

Setting

Population-based cohort, German Neonatal Network (GNN).

Population

6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth).

Methods

Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age.

Results

PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes.

Conclusions

The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.     

Examination of the Relationship between Oral Health and Arterial Sclerosis without Genetic Confounding through the Study of Older Japanese Twins

ObjectiveAlthough researchers have recently demonstrated a relationship between oral health and arterial sclerosis, the genetic contribution to this relationship has been ignored even though genetic factors are expected to have some effect on various diseases. The aim of this study was to evaluate oral health as a significant risk factor related to arterial sclerosis after eliminating genetic confounding through study of older Japanese twins.ResultsWe examined 91 monozygotic and 15 dizygotic twin pairs (males: 42, females: 64) with a mean (± standard deviation) age of 67.4 ± 10.0 years. Out of all of the oral health-related measurements collected, only the number of teeth was significantly related to arterial sclerosis (odds ratio: 0.72, 95% confidence interval: 0.52-0.99 per five teeth). Regression analysis showed a significant association between the IMT-Cmax and the number of teeth as an environmental factor (p = 0.037).ConclusionsAnalysis of monozygotic twins older than 50 years of age showed that having fewer teeth could be a significant environmental factor related to arterial sclerosis, even after controlling for genetic and familial confounding.     

基于VTK和MFC的医学图像三维重建研究与实现

VTK是医学可视化领域的主流工具,MFC是Windows平台下的应用程序框架。尝试将两者进行结合编程,以实现二维医学图像的三维重建。实现医学图像三维重建的主要方法是面绘制和体绘制。将利用多组医学图像数据进行三维重建研究,其中面绘制用移动立方体法,体绘制用光线投射法、最大密度投影法和合成体绘制法实现。最后比较两种绘制技术的结果并讨论了它们的特点。结果表明,VTK作为一种图像处理和三维可视化工具其功能是十分强大的。