Factors influencing referrals for ultrasound-diagnosed complications during prenatal care in five low and middle income countries

Background

Ultrasound during antenatal care (ANC) is proposed as a strategy for increasing hospital deliveries for complicated pregnancies and improving maternal, fetal, and neonatal outcomes. The First Look study was a cluster-randomized trial conducted in the Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia to evaluate the impact of ANC-ultrasound on these outcomes. An additional survey was conducted to identify factors influencing women with complicated pregnancies to attend referrals for additional care.

Methods

Women who received referral due to ANC ultrasound findings participated in structured interviews to characterize their experiences. Cochran-Mantel-Haenszel statistics were used to examine differences between women who attended the referral and women who did not. Sonographers’ exam findings were compared to referred women’s recall.

Results

Among 700 referred women, 510 (71%) attended the referral. Among referred women, 97% received a referral card to present at the hospital, 91% were told where to go in the hospital, and 64% were told that the hospital was expecting them. The referred women who were told who to see at the hospital (88% vs 66%), where to go (94% vs 82%), or what should happen, were more likely to attend their referral (68% vs 56%). Barriers to attending referrals were cost, transportation, and distance. Barriers after reaching the hospital were substantial. These included not connecting with an appropriate provider, not knowing where to go, and being told to return later. These barriers at the hospital often led to an unsuccessful referral.

Conclusions

Our study found that ultrasound screening at ANC alone does not adequately address barriers to referrals. Better communication between the sonographer and the patient increases the likelihood of a completed referral. These types of communication include describing the ultrasound findings, including the reason for the referral, to the mother and staff; providing a referral card; describing where to go in the hospital; and explaining the procedures at the hospital. Thus, there are three levels of communication that need to be addressed to increase completion of appropriate referrals-communication between the sonographer and the woman, the sonographer and the clinic staff, and the sonographer and the hospital.

Trial registration

NCT01990625.

     

A Preliminar y Study on Combination Therapy of Artemisinin Dimer Oxime and Topotecan against Nonsmall Cell Lung Cancer in Mice

Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor?derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells(NCI?H640, 1 × 107 in 100 μL) are implanted subcutaneously, or 1 × 107 in 50 μL in the thoracic cavity, in athymic nude mice(nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment(dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action.     

Polychromatic flow cytometric high-throughput assay to analyze the innate immune response to Toll-like receptor stimulation

Polychromatic flow cytometry allows the capture of multidimensional data, providing the technical tool to assess complex immune responses. Interrogation of the adaptive T cell response to infection or vaccination already has benefited greatly from standardized protocols for polychromatic flow cytometric analysis. The innate immune system plays an important role in health and disease, and presents potentially important therapeutic and diagnostic modalities. We describe here a high-throughput polychromatic flow cytometry-based platform that enables the rapid interrogation and large scale screening of human blood antigen presenting cell responses to Toll-like receptor (TLR) ligands and other innate immune modulators. Using this assay, we found that for certain stimuli (e.g., TLR9 and TLR3 ligands), the general protocol for intracellular cytokine cytometry had to be significantly modified to allow response detection. Furthermore, high concentrations of TLR7/8 and TLR4 stimuli caused substantial changes in lineage markers, potentially confounding analysis if one were to use a conventional "lineage-negative" cocktail. The assay we developed is reproducible and has been used to show that a given individual's TLR response pattern is relatively stable over at least several months. This protocol is in strict compliance with published guidelines for polychromatic flow cytometry, provides a common platform for scientists to compare their results directly, and may be applicable to the diagnostic evaluation of Toll-like receptor function and the rapid screening of promising therapeutic innate immune modulators.     

An asthmatic adolescent with hematuria and hemoptysis

When alveolar hemorrhage occurs in association with glomerulonephritis, one of the leading causes is Goodpasture syndrome. We report a case of an adolescent who presented to the emergency department in respiratory distress. Subsequent evaluation was consistent with the diagnosis of Goodpasture syndrome.     

SERCA2a Gene Transfer Enhances eNOS Expression and Activity in Endothelial Cells

Congestive heart failure (HF) is associated with impaired endothelium-dependent nitric oxide–mediated vasodilatation. The aim of this study was to examine the effects of sarco/endoplasmic reticulum (ER) Ca²⁺-ATPase 2a (SERCA2a) gene transfer on endothelial function in a swine HF model. Two months after the creation of mitral regurgitation to induce HF, the animals underwent intracoronary injection of adeno-associated virus (AAV) carrying SERCA2a (n = 7) or saline (n = 6). At 4 months, coronary flow (CF) was measured in the mid-portion of the left anterior descending (LAD) artery. In the failing animals, CF was decreased significantly; SERCA2a gene transfer rescued CF to levels observed in sham-group [ml/min/g, 0.47 ± 0.064 saline versus 0.89 ± 0.116, SERCA2a; P < 0.05; 1.00 ± 0. 185 sham P = NS (nonsignificant)]. In coronary arteries from HF animals, SERCA2a and endothelial isoform of nitric oxide synthase (eNOS) protein expression were decreased, but restored to normal levels by SERCA2a gene transfer. In human coronary artery endothelial cells (HCAECs), SERCA2a overexpression increased eNOS expression, phosphorylation, eNOS promoter activity, Ca²⁺ storage capacity, and enhanced histamine-induced calcium oscillations, eNOS activity, and cyclic guanosine monophosphate (cGMP) production. Thus, SERCA2a gene transfer increases eNOS expression and activity by modulating calcium homeostasis to improve CF. These findings suggest that SERCA2a gene transfer improves vascular reactivity in the setting of HF.     

Subglottic carcinoma treated with surgery and adjuvant photodynamic therapy

Subglottic cancers are extremely rare as a primary malignancy representing <8% of all laryngeal cancers. Typical age at presentation is in the 5th decade. There are three main types of subglottic carcinoma: adenocarcinoma, mucoepidermoid and adenoid cystic carcinoma. We present a rare case of subglottic cancer treated with surgery and adjuvant photodynamic therapy.     

Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954 → Leu substitution in the factor VIII A3 domain

In some families with mild haemophilia higher results are obtained for factor VIII activity (FVII:C) determined by one-stage assay than by two-stage or chromogenic assays. Amino-acid substitutions in the A1, A2 and A3 domains of factor VIII have been described in affected individuals with this phenotype. We describe a case of mild haemophilia A in which FVIII:C measured by one-stage assay was normal at 106%. However, FVIII:C levels measured by two-stage and chromogenic assays were 18% and 35% respectively. DNA analysis revealed a novel mutation in the A3 domain of factor VIII, His1954-->Leu. In a molecular model of the FVIII A domains, His1954 is placed in close proximity to two other mutations that have previously been shown also to be associated with one-stage/two-stage discrepancies. In this patient the diagnosis of haemophilia A would be missed if only the one-stage assay was used.     

Percutaneous intramedullary elastic wiring of displaced diaphyseal forearm fractures in children. A modified technique.

Under the age of 11 years there are specific anatomic considerations which favour intramedullary wiring of displaced forearm fractures. The isthmus of radius and ulna is narrow (range = 3-6 mm). The medulla is at its widest proximally in the (ulna) and distally in the radius. These are the optimum entry points for intramedullary progression of the wire. At these points there is a low stress raising effect minimising the risk of iatrogenic fracture. A 1.6 mm Kirschner wire is elastic enough to be prebent into a large radius. It is strong enough to resist deformity on entry, though elastic enough to achieve stability by intramedullary three-point contact. The tip of the wire is prebent to 30 degrees aiding closed reduction of displaced fractures. An oblique 4.5 mm drill hole is made through a < 2 cm skin incision avoiding the epiphysis. This allows the wire to be introduced into the intramedullary canal at an optimum angle of 30 degrees. A smaller hole would not allow intramedullary progression e.g.; in a 2.5 mm hole the angle of insertion would be 55 degrees. Wire is now held with a cannulated T-handle, which is tapped with a hammer thus bouncing the wire of the side wall into the medulla. Rotating the handle aids reducing of displaced fractures. There are advantages to this method over other methods of intramedullary fixation e.g.; Steinman pins, Rush pins, or Nancy nails. Also holds advantage over plating. Over the last 12 months 11 cases were treated by the above methods without significant complications.     

Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial

Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.