2009 Pandemic Influenza A (H1N1) Virus Outbreak and Response – Rwanda, October, 2009–May, 2010

BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1)pdm09 (pH1N1) was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL). Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532) of specimens tested influenza positive; of these 96% (n = 510) were influenza A and 4% (n = 22) were influenza B. Of cases testing influenza A positive, 96.8% (n = 494), 3% (n = 15), and 0.2% (n = 1) were A(H1N1)pdm09, Seasonal A(H3) and Seasonal A(non-subtyped), respectively. Among laboratory-confirmed cases, 263 (53.2%) were children <15 years and 275 (52%) were female. In total, 58 (12%) cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days). All cases recovered and there were no deaths. Overall, 339 (68%) confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532) were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532), asthma 0.8% (4/532), cardiac disease 1.5% (8/532), pregnancy 0.6% (3/532), diabetes mellitus 0.4% (2/532), and chronic malnutrition 0.8% (4/532). CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to strengthen integrated disease surveillance, develop laboratory contingency plans, and evaluate the influenza sentinel surveillance system

Four-Year Treatment Outcomes of Adult Patients Enrolled in Mozambique's Rapidly Expanding Antiretroviral Therapy Program

BACKGROUND: In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004-2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4(+) T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3-1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6-2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. CONCLUSIONS: ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed

Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy

Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' — a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed

Effect of Crowd Composition on the Wisdom of Artificial Crowds Metaheuristic

This paper investigates the impact that task difficulty and crowd composition have on the success of the Wisdom of Artificial Crowds metaheuristic. The metaheuristic, which is inspired by the wisdom of crowds phenomenon, combines the intelligence from a group of optimization searches to form a new solution. Unfortunately, the aggregate formed by the metaheuristic is not always better than the best individual solution within the crowd, and little is known about the variables which maximize the metaheuristic\u27s success. Our study offers new insights into the influential factors of artificial crowds and the collective intelligence of multiple optimization searches performed on the same problem. The results show that favoring the opinions of experts (i.e., the better searches) improves the chances of the metaheuristic succeeding by more than 15% when compared to the traditional means of equal weighting. Furthermore, weighting expertise was found to require smaller crowd sizes for the metaheuristic to reach its peak chances of success. Finally, crowd size was discovered to be a critical factor, especially as problem complexity grows or average crowd expertise declines. However, crowd size matters only up to a point, after which the probability of success plateaus

Development and validation of a nomogram for urothelial cancer in patients with chronic kidney disease

Abstract Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24–10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67–2.35). A nomogram based on patients’ age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86–0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review.

The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB