Testing positive pressure delivered from commercial and WHO-style pediatric bubble CPAP devices.

BACKGROUND/AIM: Low-cost commercial bCPAP devices have been deployed in resource-limited settings to treat neonatal respiratory failure. The use of these devices has increased access to pediatric respiratory support for infants. However, constrained resources may result in substitution of recommended consumables and/or use in older age groups. We hypothesized that commercially available bCPAP devices, the standard WHO-style device and various improvised adaptations would all generate effective, safe positive pressure at the patient interface. METHODS: Performance of 2 commercially available bCPAP devices was tested against the standard WHO-style bCPAP device, as well as several improvised modifications of these devices, by measuring positive pressure delivered at the patient interface. Variables tested included different flow rates, patient interfaces and respiratory circuit tubing. RESULTS: Both commercial devices utilized according to manufacturer recommendations generated the expected positive pressure at the patient interface. When testing the recommended WHO-style bCPAP device with recommended materials as well as other improvised modifications, we found variable and potentially unpredictable generation of positive pressure at the patient interface. CONCLUSIONS: Modified or improvised bCPAP devices should be used with extreme caution as the support provided may be more or less than expected depending on respiratory tubing and flow rates employed. Our data support the effectiveness of bCPAP in newborns and young infants. But, to our knowledge, there are no bCPAP patient interfaces for older children effective with low liter flow devices. Therefore, based on these results, we recommend against using WHO-style bCPAP devices for non-infant patients with respiratory failure and instead recommend using standard oxygen therapy with nasal cannulae or face-masks, as well as early consideration of transfer to a higher level of care.

Cash interventions to improve clinical outcomes for pulmonary tuberculosis: systematic review and meta-analysis.

OBJECTIVE: To assess cash transfer interventions for improving treatment outcomes of active pulmonary tuberculosis in low- and middle-income countries. METHODS: We searched PubMed®, Embase®, Cochrane Library and ClinicalTrials.gov for studies published until 4 August 2017 that reported on cash transfer interventions during the treatment of active pulmonary tuberculosis in low- and middle-income countries. Our primary outcome was a positive clinical outcome, defined as treatment success, treatment completion or microbiologic cure. Using the purchasing power parity conversion factor, we converted the amount of cash received per patient within each study into international dollars (Int$). We calculated odds ratio (OR) for the primary outcome using a random effects meta-analysis. FINDINGS: Eight studies met eligibility criteria for review inclusion. Seven studies assessed a tuberculosis-specific intervention, with average amount of cash ranging from Int$ 193-858. One study assessed a tuberculosis-sensitive intervention, with average amount of Int$ 101. Four studies included non-cash co-interventions. All studies showed better primary outcome for the intervention group than the control group. After excluding three studies with high risk of bias, patients receiving tuberculosis-specific cash transfer were more likely to have a positive clinical outcome than patients in the control groups (OR: 1.77; 95% confidence interval: 1.57-2.01). CONCLUSION: The evidence available suggests that patients in low- and middle-income countries receiving cash during treatment for active pulmonary tuberculosis are more likely to have a positive clinical outcome. These findings support the incorporation of cash transfer interventions into social protection schemes within tuberculosis treatment programmes.

Successful implementation of a combined learning collaborative and mentoring intervention to improve neonatal quality of care in rural Rwanda.

BACKGROUND: Globally, neonatal mortality remains high despite interventions known to reduce neonatal deaths. The All Babies Count (ABC) initiative was a comprehensive health systems strengthening intervention designed by Partners In Health in collaboration with the Rwanda Ministry of Health to improve neonatal care in rural public facilities. ABC included provision of training, essential equipment, and a quality improvement (QI) initiative which combined clinical and QI mentorship within a learning collaborative. We describe ABC implementation outcomes, including development of a QI change package. METHODS: ABC was implemented over 18 months from 2013 to 2015 in two Rwandan districts of Kirehe and Southern Kayonza, serving approximately 500,000 people with 24 nurse-led health centers and 2 district hospitals. A process evaluation of ABC implementation and its impact on healthcare worker (HCW) attitudes and QI practice was done using program documents, standardized surveys and focus groups with facility QI team members attending ABC Learning Sessions. The Change Package was developed using mixed methods to identify projects with significant change according to quantitative indicators and qualitative feedback obtained during focus group discussions. Outcome measures included ABC implementation process measures, HCW-reported impact on attitudes and practice of QI, and resulting change package developed for antenatal care, delivery management and postnatal care. RESULTS: ABC was implemented across all 26 facilities with an average of 0.76 mentorship visits/facility/month and 118 tested QI change ideas. HCWs reported a reduction in barriers to quality care delivery related to training (p = 0.018); increased QI capacity (knowledge 37 to 89%, p <  0.001); confidence (47 to 89%, p <  0.001), QI leadership (59 to 91%, p <  0.001); and peer-to-peer learning (37 to 66%, p = 0.024). The final change package included 46 change ideas. Themes associated with higher impact changes included provision of mentorship and facility readiness support through equipment provision. CONCLUSIONS: ABC provides a feasible model of an integrated approach to QI in rural Rwanda. This model resulted in increases in HCW and facility capacity to design and implement effective QI projects and facilitated peer-to-peer learning. ABC and the change package are being scaled to accelerate improvement in neonatal outcomes.

Influence of strain on proteoglycan synthesis by valvular interstitial cells in three-dimensional culture.

Differently loaded regions of the mitral valve contain distinct amounts and types of proteoglycans (PGs); these PG profiles are altered in abnormal loading and disease conditions. We developed an in vitro three-dimensional model to analyze PGs secreted by valvular interstitial cells (VICs) isolated from distinct regions of porcine mitral valves (leaflet or chordae) and subjected to either biaxial or uniaxial mechanical constraints. In addition, the PGs, DNA and collagen content of the collagen gels was monitored over time. All three PGs previously found in heart valves (decorin, biglycan and versican) were present in the collagen gels and the conditioned medium. Compared to unconstrained gels, the constrained collagen gels (whether biaxially or uniaxially loaded) retained more decorin and biglycan but less versican. However, the conditioned medium from constrained collagen gels contained higher amounts of all three PGs than did medium from unconstrained gels. Constrained collagen gels containing leaflet cells retained more decorin and biglycan than did those containing chordal cells. DNA content was maintained early in the culture period but was reduced by 55-80% after 7 days, whereas PG synthesis increased over time. At the end of the culture period, the cell density was highest in the biaxial region of gels seeded with leaflet cells. In contrast, collagen content in both constrained and unconstrained gels remained consistent over culture duration. This study provides valuable information about the role of applied loading on proteoglycan segregation, which should aid in tissue engineering applications and for understanding valve biology and pathology.

Experience: developing an inpatient malnutrition checklist for children 6 to 59 months to improve WHO protocol adherence and facilitate quality improvement in a low-resource setting.

In low-resource settings, inpatient case fatality for severe acute malnutrition (SAM) remains high despite evidenced-based protocols and resources to treat SAM. Key reasons include a combination of insufficiently trained staff, poor teamwork and inadequate compliance to WHO treatment guidelines which are proven to reduce mortality. Checklists have been used in surgery and obstetrics to ameliorate similarly complicated yet repetitive work processes and may be a key strategy to improving inpatient SAM protocol adherence and reducing unnecessary death. Here, we share our experience developing and piloting an inpatient malnutrition checklist (MLNC) for children 6 to 59 months and associated scoring system to coordinate care delivery, improve team documentation, strengthen WHO malnutrition protocol adherence and facilitate quality improvement in a district hospital in rural Rwanda. MLNC was developed after careful review of the 2009 Rwandan National Nutrition Protocol and 2013 WHO malnutrition guidelines. Critical steps were harmonized, extracted and designed into an initial MLNC with input from pediatric ward nurses, doctors, a locally based pediatrician and a registered dietitian. A scoring system was developed to facilitate quality improvement. Using the standard Plan-Do-Study-Act cycle, MLNC was modified and progress assessed on a monthly to bimonthly basis. Significant modifications occurred in the first 6 months of piloting including incorporation of treatment reminders and formatting improvements, as well as initiation of the MLNC from the emergency department. The MLNC is the first checklist to be developed that unifies WHO 10 steps of treatment of inpatient SAM with local standards. Anecdotally, MLNC was observed to identify gaps in key malnutrition care, promote protocol adherence and facilitate quality improvement. Data gathering on the MLNC local facility impact is underway. Collaborative international efforts are needed to create an inpatient malnutrition checklist for wider use to improve quality and reduce unnecessary, facility-based child mortality.

Synthesis of glycosaminoglycans in differently loaded regions of collagen gels seeded with valvular interstitial cells.

Cells respond to changes in mechanical strains by varying their production of extracellular matrix macromolecules. Because differences in strain patterns between mitral valve leaflets and chordae tendineae have been linked to different quantities and types of glycosaminoglycans (GAGs), we investigated the effects of various strain conditions on GAG synthesis by valvular interstitial cells (VICs) using an in vitro 3-dimensional tissue-engineering model. VICs from leaflets or chordae were seeded within collagen gels and subjected to uniaxial or biaxial static tension for 1 week. GAGs synthesized within the collagen gels and secreted into the surrounding medium were analyzed using fluorophore-assisted carbohydrate electrophoresis. In constrained conditions, more 4-sulfated GAGs were retained within the collagen gel, whereas more hyaluronan was secreted into the surrounding medium. Selected GAG classes were found in significantly different proportions in collagen gels seeded with leaflet cells versus chordal cells. The only significant difference between uniaxial and biaxial regions was found for 6-sulfated GAGs in the gels seeded with chordal cells (p<0.05). This study suggests how mechanical loading may influence GAG production and localization in the remodeling of the mitral valve and has design implications for engineered tissues.

Experiencing antiretroviral adherence: helping healthcare staff better understand adherence to paediatric antiretrovirals.

BACKGROUND: Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. METHODS: Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. RESULTS: The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family/friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. CONCLUSIONS: Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.

Reversible secretion of glycosaminoglycans and proteoglycans by cyclically stretched valvular cells in 3D culture.

Mitral valve leaflets and chordae have been shown to contain different amounts and proportions of glycosaminoglycans (GAGs) and proteoglycans (PGs) corresponding to in vivo normal or diseased cyclic strain patterns. To understand the effect of cyclic strains on GAG/PG synthesis by valvular interstitial cells (VICs) isolated from valve leaflet and chordae separately, porcine VICs were seeded within collagen gels and alternately stretched or relaxed for 24 h periods for one week in a custom-designed tissue engineering bioreactor. We found cyclic-stretch-induced upregulation of total GAGs and of individual GAG classes secreted into the culture medium. Leaflet cells showed a delayed response to stretching compared to chordal cells, but altered the proportions of various GAG classes they secreted during the culture duration. Decorin and biglycan PGs were slightly responsive to stretch. We demonstrated that mechanical stretch and relaxation conditions reversibly regulate GAG and PG production in a novel 3D model of valve tissues. This is the first study using cyclic strains to modulate GAG/PG synthesis by valve cells and our results may have implications for the remodeling of the mitral valve as well as other tissues.