A Comparison of the Effect of Intermittent and Continuous Infusion of Meropenem on the Prevalence of Nausea in Pediatric Cystic Fibrosis Patients

Cystic Fibrosis (CF) is a genetic disease, leading to changes of membrane secretions causing obstruction of smaller airways. CF patients often develop pulmonary infections and require antibiotic treatment. Meropenem is a broad spectrum beta lactam that acts by lysing microbes through interfering with bacterial cell wall synthesis. Although a safe and effective treatment, data on pediatric patients is limited

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence

Состояние провоспалительного цитокинового звена у больных с нестабильной стенокарадией и сахарным диабетом 2-го типа в зависимости от функционального класса хронической сердечной недостаточности

Проанализировано состояние провоспалительного звена цитокинов у больных с нестабильной стенокардией (НС) и сопутствующим сахарным диабетом (СД) 2−го типа в зависимости от функционального класса хронической сердечной недостаточности (ХСН). Нарастание проявлений сердечной декомпенсации у больных с НС и СД 2−го типа ассоциируется с высокой активностью провоспалительного цитокинового звена, представленного фактором некроза опухолей−α и интерлейкином−6. Повышение функционального класса ХСН характеризуется увеличением инсулинорезистентности у больных с НС и СД 2−го типа.Проаналізовано стан прозапальної ланки цитокінів у хворих із нестабільною стенокардією (НС) та супутнім цукровим діабетом (ЦД) 2−го типу залежно від функціонального класу хронічної серцевої недостатності (ХСН). Наростання проявів серцевої декомпенсації у хворих із НС та СД 2−го типу асоціюється з високою активністю прозапальної цитокінової ланки, представленої фактором некрозу пухлин−α та інтерлейкіном−6. Підвищення функціонального класу ХСН характеризується зростанням інсулінорезистентності у хворих із НС та ЦД 2−го типу.The state of pro−inflammatory cytokines in patients with unstable angina (UA) and associated type 2 diabetes mellitus (DM) was analyzed depending on the functional class of chronic heart failure (CHF). The increase in manifestations of cardiac decompensation in patients with UA and type 2 DM is associated with high activity of pro−inflammatory cytokine level represented by tumor necrosis factor−β and interleukin−6. Increase of functional class of CHF is characterized by increased insulin resistance in patients with UA and type 2 DM

A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P 16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

How urban characteristics affect vulnerability to heat and cold: a multi-country analysis.

BACKGROUND: The health burden associated with temperature is expected to increase due to a warming climate. Populations living in cities are likely to be particularly at risk, but the role of urban characteristics in modifying the direct effects of temperature on health is still unclear. In this contribution, we used a multi-country dataset to study effect modification of temperature-mortality relationships by a range of city-specific indicators. METHODS: We collected ambient temperature and mortality daily time-series data for 340 cities in 22 countries, in periods between 1985 and 2014. Standardized measures of demographic, socio-economic, infrastructural and environmental indicators were derived from the Organisation for Economic Co-operation and Development (OECD) Regional and Metropolitan Database. We used distributed lag non-linear and multivariate meta-regression models to estimate fractions of mortality attributable to heat and cold (AF%) in each city, and to evaluate the effect modification of each indicator across cities. RESULTS: Heat- and cold-related deaths amounted to 0.54% (95% confidence interval: 0.49 to 0.58%) and 6.05% (5.59 to 6.36%) of total deaths, respectively. Several city indicators modify the effect of heat, with a higher mortality impact associated with increases in population density, fine particles (PM2.5), gross domestic product (GDP) and Gini index (a measure of income inequality), whereas higher levels of green spaces were linked with a decreased effect of heat. CONCLUSIONS: This represents the largest study to date assessing the effect modification of temperature-mortality relationships. Evidence from this study can inform public-health interventions and urban planning under various climate-change and urban-development scenarios