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author:("banzi, S")
1.  Inflammation-mediated rheumatic diseases and atherosclerosis 
Annals of the Rheumatic Diseases  2000;59(5):321-325.
PMCID: PMC1753135  PMID: 10784507
2.  Protocol for the evaluation of a free health insurance card scheme for poor pregnant women in Mbeya region in Tanzania: a controlled-before and after study 
The use of demand-side financing mechanisms to increase health service utilisation among target groups and enhance service quality is gaining momentum in many low- and middle-income countries. However, there is limited evidence on the effects of such schemes on equity, financial protection, quality of care, and cost-effectiveness. A scheme providing free health insurance cards to poor pregnant women and their households was first introduced in two regions of Tanzania in 2011 and gradually expanded in 2012.
A controlled before and after study will examine in one district the effect of the scheme on utilization, quality, and cost of healthcare services accessed by poor pregnant women and their households in Tanzania. Data will be collected 4 months before implementation of the scheme and 17 months after the start of implementation from a survey of 24 health facilities, 288 patients exiting consultations and 1500 households of women who delivered in the previous year in one intervention district (Mbarali). 288 observations of provider-client interactions will also be carried out. The same data will be collected from a comparison district in a nearby region. A process evaluation will ascertain how the scheme is implemented in practice and the level of implementation fidelity and potential moderators. The process evaluation will draw from impact evaluation data and from three rounds of data collection at the national, regional, district, facility and community levels. An economic evaluation will measure the cost-effectiveness of the scheme relative to current practice from a societal perspective.
This evaluation will generate evidence on the impact and cost-effectiveness of targeted health insurance for pregnant women in a low income setting, as well as building a better understanding of the implementation process and challenges for programs of this nature.
PMCID: PMC4490646  PMID: 26141724
Demand-side financing; Health insurance; Maternal health; Poverty; Impact evaluation; Process evaluation; Economic evaluation
3.  Access to CD4 Testing for Rural HIV Patients: Findings from a Cohort Study in Zimbabwe 
PLoS ONE  2015;10(6):e0129166.
CD4 cell count measurement remains an important diagnostic tool for HIV care in developing countries. Insufficient laboratory capacity in rural Sub-Saharan Africa is frequently mentioned but data on the impact at an individual patient level are lacking. Urban-rural discrepancies in CD4 testing have not been quantified to date. Such evidence is crucial for public health planning and to justify new yet more expensive diagnostic procedures that could circumvent access constraints in rural areas.
To compare CD4 testing among rural and urban HIV patients during the first year of treatment.
Records from 2,145 HIV positive adult patients from a Médecins sans Frontières (Doctors without Borders) HIV project in Beitbridge, Zimbabwe, during 2011 and 2012 were used for a retrospective cohort analysis. Covariate-adjusted risk ratios were calculated to estimate the effects of area of residence on CD4 testing at treatment initiation, six and 12 months among rural and urban patients.
While the proportion of HIV patients returning for medical consultations at six and 12 months decreased at a similar rate in both patient groups, CD4 testing during consultations dropped to 21% and 8% for urban, and 2% and 1% for rural patients at six and 12 months, respectively. Risk ratios for missing CD4 testing were 0.8 (95% CI 0.7-0.9), 9.2 (95% CI 5.5-15.3), and 7.6 (95% 3.7-17.1) comparing rural versus urban patients at treatment initiation, six and 12 months, respectively.
CD4 testing was low overall, and particularly poor in rural patients. Difficulties with specimen transportation were probably a major factor underlying this difference and requires new diagnostic approaches. Our findings point to severe health system constraints in providing CD4 testing overall that need to be addressed if effective monitoring of HIV patients is to be achieved, whether by alternative CD4 diagnostics or newly-recommended routine viral load testing.
PMCID: PMC4471276  PMID: 26083342
5.  Accuracy of magnetic resonance cholangiography compared to operative endoscopy in detecting biliary stones, a single center experience and review of literature 
World Journal of Radiology  2015;7(4):70-78.
AIM: To compare diagnostic sensitivity, specificity and accuracy of magnetic resonance cholangiopancreatography (MRCP) without contrast medium and endoscopic ultrasound (EUS)/endoscopic retrograde cholangiopancreatography (ERCP) for biliary calculi.
METHODS: From January 2012 to December 2013, two-hundred-sixty-three patients underwent MRCP at our institution, all MRCP procedure were performed with the same machinery. In two-hundred MRCP was done for pure hepatobiliary symptoms and these patients are the subjects of this study. Among these two-hundred patients, one-hundred-eleven (55.5%) underwent ERCP after MRCP. The retrospective study design consisted in the systematic revision of all images from MRCP and EUS/ERCP performed by two radiologist with a long experience in biliary imaging, an experienced endoscopist and a senior consultant in Hepatobiliopancreatic surgery. A false positive was defined an MRCP showing calculi with no findings at EUS/ERCP; a true positive was defined as a concordance between MRCP and EUS/ERCP findings; a false negative was defined as the absence of images suggesting calculi at MRCP with calculi localization/extraction at EUS/ERCP and a true negative was defined as a patient with no calculi at MRCP ad at least 6 mo of asymptomatic follow-up. Biliary tree dilatation was defined as a common bile duct diameter larger than 6 mm in a patient who had an in situ gallbladder. A third blinded radiologist who examined the MRCP and ERCP data reviewed misdiagnosed cases. Once obtained overall data on sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) we divided patients in two groups composed of those having concordant MRCP and EUS/ERCP (Group A, 72 patients) and those having discordant MRCP and EUS/ERCP (Group B, 20 patients). Dataset comparisons had been made by the Student’s t-test and χ2 when appropriate.
RESULTS: Two-hundred patients (91 men, 109 women, mean age 67.6 years, and range 25-98 years) underwent MRCP. All patients attended regular follow-up for at least 6 mo. Morbidity and mortality related to MRCP were null. MRCP was the only exam performed in 89 patients because it did show only calculi into the gallbladder with no signs of the presence of calculi into the bile duct and symptoms resolved within a few days or after colecistectomy. The patients remained asymptomatic for at least 6 mo, and we assumed they were true negatives. One hundred eleven (53 men, 58 women, mean age 69 years, range 25-98 years) underwent ERCP following MRCP. We did not find any difference between the two groups in terms of race, age, and sex. The overall median interval between MRCP and ERCP was 9 d. In detecting biliary stones MRCP Sensitivity was 77.4%, Specificity 100% and Accuracy 80.5% with a PPV of 100% and NPV of 85%; EUS showed 95% sensitivity, 100% specificity, 95.5% accuracy with 100% PPV and 57.1% NPV. The association of EUS with ERCP performed at 100% in all the evaluated parameters. When comparing the two groups, we did not find any statistically significant difference regarding age, sex, and race. Similarly, we did not find any differences regarding the number of extracted stones: 116 stones in Group A (median 2, range 1 to 9) and 27 in Group B (median 2, range 1 to 4). When we compared the size of the extracted stones we found that the patients in Group B had significantly smaller stones: 14.16 ± 8.11 mm in Group A and 5.15 ± 2.09 mm in Group B; 95% confidence interval = 5.89-12.13, standard error = 1.577; P < 0.05. We also found that in Group B there was a significantly higher incidence of stones smaller than 5 mm: 36 in Group A and 18 in Group B, P < 0.05.
CONCLUSION: Major finding of the present study is that choledocholithiasis is still under-diagnosed in MRCP. Smaller stones (< 5 mm diameter) are hardly visualized on MRCP.
PMCID: PMC4404370  PMID: 25918584
Biliary strictures; Magnetic resonance cholangiopancreatography; Biliary stones; Endoscopic retrograde cholangiopancreatography; Endoscopic ultrasound
6.  Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C 
Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.
Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.
Mean measured GFRs were 68 and 70 ml per minute per 1.73 m2 of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m2 with the creatinine equation and the cystatin C equation (P = 0.07 and P = 0.05), respectively. Precision was improved with the combined equation (inter-quartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m2, respectively [P = 0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m2, the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m2 or greater than or equal to 60 ml per minute per 1.73 m2 (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2.
The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)
PMCID: PMC4398023  PMID: 22762315
7.  Effects of a New Combination of Nutraceuticals with Morus alba on Lipid Profile, Insulin Sensitivity and Endotelial Function in Dyslipidemic Subjects. A Cross-Over, Randomized, Double-Blind Trial 
Nutraceuticals (NUT) are forms of compounds with biological activity commonly used to improve health in dosage largely exceeding those obtainable in food.
We compared, in a double blind randomized cross-over trial, the effects of two NUT combinations on the control of glico-lipidic metabolism in patients with hypercholesterolemia not on statins.
At study start patients were given dietary counseling and received placebo for 2 weeks. After this run-in period, patients were randomized: (1) Combination A [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine, Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A.
Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the patients, and Cambination A only in 21.7 % of them (p ≤ 0.027). Both treatments reduced plasma levels of triglycerides, total and LDL cholesterol and increased HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more pronounced in patients taking Combination B (p < 0.005). Combination B reduced also glycated hemoglobin, fasting glucose and insulin plasma levels as well as HOMA index (p < 0.005).
An increased content of Berberin and Monacolin K and the addition of Morus alba extract improves the effect on plasma cholesterol and on glucose metabolism of the NUT Combination. These effects may allow the speculation of a more marked improvement in cardiovascular prognosis.
PMCID: PMC4461797  PMID: 25870124
Nutraceuticals; Hypercholesterolemia; Insulin sensitivity
8.  WAVE binds Ena/VASP for enhanced Arp2/3 complex–based actin assembly 
Molecular Biology of the Cell  2015;26(1):55-65.
A dual in vitro/in vivo approach is used to show that WAVE directly binds Ena/VASP, coordinating its activity with that of the Arp2/3 complex for enhanced actin assembly.
The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells. Other important players in lamellipodial protrusion are Ena/VASP proteins, which enhance actin filament elongation. Here we examine the molecular coordination between the nucleating activity of the Arp2/3 complex and the elongating activity of Ena/VASP proteins for the formation of actin networks. Using an in vitro bead motility assay, we show that WAVE directly binds VASP, resulting in an increase in Arp2/3 complex–based actin assembly. We show that this interaction is important in vivo as well, for the formation of lamellipodia during the ventral enclosure event of Caenorhabditis elegans embryogenesis. Ena/VASP's ability to bind F-actin and profilin-complexed G-actin are important for its effect, whereas Ena/VASP tetramerization is not necessary. Our data are consistent with the idea that binding of Ena/VASP to WAVE potentiates Arp2/3 complex activity and lamellipodial actin assembly.
PMCID: PMC4279229  PMID: 25355952
9.  A balance between membrane elasticity and polymerization energy sets the shape of spherical clathrin coats 
Nature Communications  2015;6:6249.
In endocytosis, scaffolding is one of the mechanisms to create membrane curvature by moulding the membrane into the spherical shape of the clathrin cage. However, the impact of membrane elastic parameters on the assembly and shape of clathrin lattices has never been experimentally evaluated. Here, we show that membrane tension opposes clathrin polymerization. We reconstitute clathrin budding in vitro with giant unilamellar vesicles (GUVs), purified adaptors and clathrin. By changing the osmotic conditions, we find that clathrin coats cause extensive budding of GUVs under low membrane tension while polymerizing into shallow pits under moderate tension. High tension fully inhibits polymerization. Theoretically, we predict the tension values for which transitions between different clathrin coat shapes occur. We measure the changes in membrane tension during clathrin polymerization, and use our theoretical framework to estimate the polymerization energy from these data. Our results show that membrane tension controls clathrin-mediated budding by varying the membrane budding energy.
A relationship between membrane tension and clathrin polymerization during endocytosis has not been experimentally established. Here, the authors show using an in vitro reconstituted system and theoretical modelling that membrane tension regulates clathrin polymerization into spherical cages by varying the membrane budding energy.
PMCID: PMC4346611  PMID: 25695735
10.  Dialogue: Vitamin D, statins and atherosclerotic progression in paediatric lupus 
Lupus Science & Medicine  2015;2(1):e000081.
PMCID: PMC4322310  PMID: 25685366
Autoimmunity; Atherosclerosis; Systemic Lupus Erythematosus
11.  Lymphoma risk in systemic lupus: effects of disease activity versus treatment 
Annals of the rheumatic diseases  2013;73(1):10.1136/annrheumdis-2012-202099.
To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren’s syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.
We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.
In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
PMCID: PMC3855611  PMID: 23303389
12.  Use of digital panoramic radiography as an auxiliary means of low bone mineral density detection in post-menopausal women 
Dentomaxillofacial Radiology  2013;42(10):20120059.
To correlate the radiomorphometric indices obtained using digital panoramic radiography (DPR) with bone mineral densities, evaluated by the dual-energy X-ray absorptiometry test, in a population of post-menopausal females to identify patients with asymptomatic low bone mineral densities.
The morphology of the mandibular cortex was evaluated using the mandibular cortical index (MCI) and the inferior mandibular cortex width was evaluated using the mental index (MI) in 64 female patients who had undergone dual-energy X-ray absorptiometry assessment. Of these patients, 21 were diagnosed with osteopaenia and 20 with osteoporosis, and 23 were normal. Three new indices for evaluating the inferior mandibular cortex width were designed: the mental posterior index 1 (MPI1), MPI2 and MPI3. Statistical analyses were performed using the χ2 and Kruskal–Wallis tests and the receiver operating characteristic curve.
There were significant differences between the normal and lower bone mineral density groups (osteopaenia and osteoporosis) for MCI (p < 0.01). In the osteoporosis group, the MI, MPI1, MPI2 and MPI3 were significantly different from the normal and osteopaenia groups (p < 0.05). The MI, MPI1, MPI2 and MPI3 showed that there is an area in the mandibular cortex, located between the mental foramen and the antegonial region, which is valid for identifying females at high risk for osteoporosis.
The MCI, MI, MPI1, MPI2, and MPI3 radiomorphometric indices evaluated using DPR can be used to identify post-menopausal females with low bone densities and to provide adequate medical treatment for them.
PMCID: PMC3853514  PMID: 24005062
bone density; osteoporosis; panoramic radiography; prevention; control
13.  Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking 
Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.
PMCID: PMC3785958  PMID: 24062578
acto-myosin; cortical tension; symmetry breaking; biomimetic liposome
14.  Updated Review of Complementary and Alternative Medicine Treatments for Systemic Lupus Erythematosus 
Current rheumatology reports  2013;15(11):378.
It is estimated that over 50 % of patients with systemic lupus erythematosus (SLE) have utilized complementary and alternative medicine (CAM) treatments to reduce symptoms and manage their health. However, there are relatively few randomized controlled trials of CAM for SLE. This review describes recent studies of vitamins and supplements, acupuncture, and mind-body interventions in SLE patients. The recent trials of CAM treatments for SLE indicate that supplements such as vitamin D, omega 3 fatty acids, N-acetyl cysteine and turmeric show some promise for reducing SLE disease activity. In addition, mind-body methods such as cognitive-behavioral therapy and other counseling interventions may improve mood and quality of life in SLE.
PMCID: PMC3898893  PMID: 24078104
Systemic lupus erythematosus; Complementary medicine; Alternative medicine; Integrative medicine; Supplements; Acupuncture; Vitamins; Mind–body treatments; Cognitive behavioral therapy; Meditation; Interpersonal therapy; N-acetyl cysteine; turmeric; DHEA; Vitamin D; Vitamin C; Vitamin E; Vitamin B6; Omega 3 fatty acids; Fish oil; Oxidative stress; Anti-oxidants
15.  Perivascular Adipose Tissue of the Descending Thoracic Aorta is Associated with Systemic Lupus Erythematosus and Vascular Calcification in Women 
Atherosclerosis  2013;231(1):10.1016/j.atherosclerosis.2013.09.004.
Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE-disease related risk factors do not fully account for this increased risk. Perivascular adipose tissue (PVAT) is a visceral adipose depot in close proximity to blood vessels possibly influencing CVD. We hypothesized that women with SLE have an increased volume of descending thoracic aortic PVAT (aPVAT) associated with increased vascular calcification.
Using electron beam computed tomography, we quantified the aPVAT in clinically CVD-free SLE women (n=135) and age-/race-matched healthy controls (HC, n=152). Coronary artery calcification (CAC) and aortic calcification (AC) were quantified using Agatston scores and the aPVAT was quantified using standard Hounsfield Units (HU) for adipose tissue.
Women with SLE had greater median aPVAT (32.2 cm3 vs. HC aPVAT 28.6 cm3, p=0.0071) and greater median AC (26.0 vs HC AC 6.0, p=0.0013) than the healthy control women. Total aPVAT (per 25 cm3) remained significantly associated with SLE after adjusting for CVD risk factors (Odds Ratio 1.74 [95% Confidence Interval: 1.04-2.9], p=0.034), but was attenuated when adjusting for circulating inflammatory markers (p=0.34). In a logistic regression analysis, SLE aPVAT (per 25 cm3) was associated with AC (6.78 [2.0-23], p=0.0019), which remained significant after adjusting for circulating inflammatory markers (p=0.0074), and CAC (2.66 [1.4-5.0], p=0.0028).
Total aPVAT is greater in clinically CVD-free SLE women than in age-/race-matched controls and is associated with calcification in different vascular beds.
PMCID: PMC3831349  PMID: 24125423
atherosclerosis; adipose; systemic lupus erythematosus; calcification
16.  One Size Fits All? Standardised Provision of Care for Survivors of Sexual Violence in Conflict and Post-Conflict Areas in the Democratic Republic of Congo 
PLoS ONE  2014;9(10):e111096.
Outcomes of sexual violence care programmes may vary according to the profile of survivors, type of violence suffered, and local context. Analysis of existing sexual violence care services could lead to their better adaptation to the local contexts. We therefore set out to compare the Médecins Sans Frontières sexual violence programmes in the Democratic Republic of Congo (DRC) in a zone of conflict (Masisi, North Kivu) and post-conflict (Niangara, Haut-Uélé).
A retrospective descriptive cohort study, using routine programmatic data from the MSF sexual violence programmes in Masisi and Niangara, DRC, for 2012.
In Masisi, 491 survivors of sexual violence presented for care, compared to 180 in Niangara. Niangara saw predominantly sexual violence perpetrated by civilians who were known to the victim (48%) and directed against children and adolescents (median age 15 (IQR 13–17)), while sexual violence in Masisi was more directed towards adults (median age 26 (IQR 20–35)), and was characterised by marked brutality, with higher levels of gang rape, weapon use, and associated violence; perpetrated by the military (51%). Only 60% of the patients in Masisi and 32% of those in Niangara arrived for a consultation within the critical timeframe of 72 hours, when prophylaxis for HIV and sexually transmitted infections is most effective. Survivors were predominantly referred through community programmes. Treatment at first contact was typically efficient, with high (>95%) coverage rates of prophylaxes. However, follow-up was poor, with only 49% of all patients in Masisi and 61% in Niangara returning for follow-up, and consequently low rates of treatment and/or vaccination completion.
This study has identified a number of weak and strong points in the sexual violence programmes of differing contexts, indicating gaps which need to be addressed, and strengths of both programmes that may contribute to future models of context-specific sexual violence programmes.
PMCID: PMC4203825  PMID: 25329482
17.  Non-Lymphoma Hematological Malignancies in Systemic Lupus Erythematosus 
Oncology  2013;85(4):10.1159/000350165.
To describe non-lymphoma hematological malignancies in SLE.
A large SLE cohort was linked to cancer registries. We examined the types of non-lymphoma hematological cancers.
In 16, 409 patients, 115 hematological cancers (including myelodysplastic syndrome) occurred. Among these, 33 were non-lymphoma. Of the 33 non-lymphoma cases, 13 were of lymphoid lineage: multiple myeloma (N=5), plasmacytoma (N=3), B-cell chronic lymphocytic leukemia, B-CLL (N=3), precursor cell lymphoblastic leukemia (N=1), and unspecified lymphoid leukemia (N=1). The remaining 20 cases were of myeloid lineage: myelodysplastic syndrome, MDS (N=7), acute myeloid leukemia, AML (N=7), chronic myeloid leukemia, CML (N=2), and 4 unspecified leukemias. Most of these malignancies occurred in female Caucasians, except for plasma cell neoplasms (4/5 multiple myeloma and 1/3 plasmacytoma cases occurred in blacks).
In this large SLE cohort, the most common non-lymphoma hematological malignancies were myeloid types (MDS and AML). This contrasts to the general population, where lymphoid types are 1.7 times more common than myeloid non-lymphoma hematological malignancies. Most (80%) multiple myeloma cases occurred in blacks, which requires further investigation.
PMCID: PMC3880772  PMID: 24107608
Systemic lupus erythematosus; malignancy; cancer
18.  Relation of Carotid Intima-Media Thickness and Plaque With Incident Cardiovascular Events in Women With Systemic Lupus Erythematosus 
The American journal of cardiology  2013;112(7):1025-1032.
Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p <0.01) and presence of carotid plaque (76.5% vs 30.4%, p <0.01) compared with those without incident hard CV events. Baseline carotid IMT and presence of plaque were predictive of any incident hard CV event (hazard ratio 1.35, 95% confidence interval 1.12 to 1.64, and hazard ratio 4.26, 95% confidence interval 1.23 to 14.83, respectively), independent of traditional CV risk factors and medication use. In conclusion, in women with SLE without previous CV events, carotid IMT and plaque are predictive of future CV events. This suggests that carotid ultrasound may provide an additional tool for CV risk stratification in patients with SLE.
PMCID: PMC3779482  PMID: 23827400
19.  Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements 
Lupus Science & Medicine  2014;1(1):e000056.
To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).
The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.
AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).
CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
PMCID: PMC4225732  PMID: 25396070
Autoimmune Diseases; Systemic Lupus Erythematosus; Autoantibodies
22.  5-mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities 
Molecular Brain  2014;7:67.
Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis.
Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies.
Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.
PMCID: PMC4172781  PMID: 25223405
Alcohol; 5-mehtyltetrahydrofolate; Neural crest; FASD; Xenopus
23.  Assessing predictors of delayed antenatal care visits in Rwanda: a secondary analysis of Rwanda demographic and health survey 2010 
Early initiation of antenatal care (ANC) can reduce common maternal complications and maternal and perinatal mortality. Though Rwanda demonstrated a remarkable decline in maternal mortality and 98% of Rwandan women receive antenatal care from a skilled provider, only 38% of women have an ANC visit in their first three months of pregnancy. This study assessed factors associated with delayed ANC in Rwanda.
This is a cross-sectional study using data collected during the 2010 Rwanda DHS from 6,325 women age 15–49 that had at least one birth in the last five years. Factors associated with delayed ANC were identified using a multivariable logistic regression model using manual backward stepwise regression. Analysis was conducted in Stata v12 applying survey commands to account for the complex sample design.
Several factors were significantly associated with delayed ANC including having many children (4–6 children, OR = 1.42, 95% CI: 1.22, 1.65; or more than six children, OR = 1.57, 95% CI: 1.24, 1.99); feeling that distance to health facility is a problem (OR = 1.20, 95% CI: 1.04, 1.38); and unwanted pregnancy (OR = 1.41, 95% CI: 1.26, 1.58). The following were protective against delayed ANC: having an ANC at a private hospital or clinic (OR = 0.29, 95% CI: 0.15, 0.56); being married (OR = 0.85, 95% CI: 0.75, 0.96), and having public mutuelle health insurance (OR = 0.81, 95% CI: 0.71, 0.92) or another type of insurance (OR = 0.33, 95% CI: 0.23, 0.46).
This analysis revealed potential barriers to ANC service utilization. Distance to health facility remains a major constraint which suggests a great need of infrastructure and decentralization of maternal ANC to health posts and dispensaries. Interventions such as universal health insurance coverage, family planning, and community maternal health system are underway and could be part of effective strategies to address delays in ANC.
PMCID: PMC4152595  PMID: 25163525
Antenatal care; Delayed; Demographic survey; Rwanda; Predictors
24.  The use of continuous surveys to generate and continuously report high quality timely maternal and newborn health data at the district level in Tanzania and Uganda 
The lack of high quality timely data for evidence-informed decision making at the district level presents a challenge to improving maternal and newborn survival in low income settings. To address this problem, the EQUIP project (Expanded Quality Management using Information Power) implemented a continuous household and health facility survey for continuous feedback of data in two districts each in Tanzania and Uganda as part of a quality improvement innovation for mothers and newborns.
Within EQUIP, continuous survey data were used for quality improvement (intervention districts) and for effect evaluation (intervention and comparison districts). Over 30 months of intervention (November 2011 to April 2014), EQUIP conducted continuous cross-sectional household and health facility surveys using 24 independent probability samples of household clusters to represent each district each month, and repeat censuses of all government health facilities. Using repeat samples in this way allowed data to be aggregated at six four-monthly intervals to track progress over time for evaluation, and for continuous feedback to quality improvement teams in intervention districts.
In both countries, one continuous survey team of eight people was employed to complete approximately 7,200 household and 200 facility interviews in year one. Data were collected using personal digital assistants. After every four months, routine tabulations of indicators were produced and synthesized to report cards for use by the quality improvement teams.
The first 12 months were implemented as planned. Completion of household interviews was 96% in Tanzania and 91% in Uganda. Indicators across the continuum of care were tabulated every four months, results discussed by quality improvement teams, and report cards generated to support their work.
The EQUIP continuous surveys were feasible to implement as a method to continuously generate and report on demand and supply side indicators for maternal and newborn health; they have potential to be expanded to include other health topics. Documenting the design and implementation of a continuous data collection and feedback mechanism for prospective description, quality improvement, and evaluation in a low-income setting potentially represents a new paradigm that places equal weight on data systems for course correction, as well as evaluation.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-014-0112-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4160540  PMID: 25149316
Continuous survey; Quality improvement; Maternal and newborn health; Tanzania; Uganda
25.  The reliability of a newborn foot length measurement tool used by community volunteers to identify low birth weight or premature babies born at home in southern Tanzania 
BMC Public Health  2014;14:859.
Low birthweight babies need extra care, and families need to know whether their newborn is low birthweight in settings where many births are at home and weighing scales are largely absent. In the context of a trial to improve newborn health in southern Tanzania, a counselling card was developed that incorporated a newborn foot length measurement tool to screen newborns for low birth weight and prematurity. This was used by community volunteers at home visits and shows a scale picture of a newborn foot with markers for a ‘short foot’ (<8 cm). The tool built on previous hospital based research that found newborn foot length <8 cm to have sensitivity and specificity to identify low birthweight (<2500 g) of 87% and 60% respectively.
Reliability of the tool used by community volunteers to identify newborns with short feet was tested. Between July-December 2010 a researcher accompanied volunteers to the homes of babies younger than seven days and conducted paired measures of newborn foot length using the counselling card tool and using a plastic ruler. Intra-method reliability of foot length measures was assessed using kappa scores, and differences between measurers were analysed using Bland and Altman plots.
142 paired measures were conducted. The kappa statistic for the foot length tool to classify newborns as having small feet indicated that it was moderately reliable when applied by volunteers, with a kappa score of 0.53 (95% confidence interval 0.40 – 0.66) . Examination of differences revealed that community volunteers systematically underestimated the length of newborn feet compared to the researcher (mean difference −0.26 cm (95% confidence interval −0.31—0.22), thus overestimating the number of newborns needing extra care.
The newborn foot length tool used by community volunteers to identify small babies born at home was moderately reliable in southern Tanzania where a large number of births occur at home and scales are not available. Newborn foot length is not the best anthropometric proxy for birthweight but was simple to implement at home in the first days of life when the risk of newborn death is highest.
PMCID: PMC4152587  PMID: 25142865

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