The Association between Quality of HIV Care, Loss to Follow-Up and Mortality in Pediatric and Adolescent Patients Receiving Antiretroviral Therapy in Nigeria

Access to pediatric HIV treatment in resource-limited settings has risen significantly. However, little is known about the quality of care that pediatric or adolescent patients receive. The objective of this study is to explore quality of HIV care and treatment in Nigeria and to determine the association between quality of care, loss-to-follow-up and mortality. A retrospective cohort study was conducted including patients ≤18 years of age who initiated ART between November 2002 and December 2011 at 23 sites across 10 states. 1,516 patients were included. A quality score comprised of 6 process indicators was calculated for each patient. More than half of patients (55.5%) were found to have a high quality score, using the median score as the cut-off. Most patients were screened for tuberculosis at entry into care (81.3%), had adherence measurement and counseling at their last visit (88.7% and 89.7% respectively), and were prescribed co-trimoxazole at some point during enrollment in care (98.8%). Thirty-seven percent received a CD4 count in the six months prior to chart review. Mortality within 90 days of ART initiation was 1.9%. A total of 4.2% of patients died during the period of follow-up (mean: 27 months) with 19.0% lost to follow-up. In multivariate regression analyses, weight for age z-score (Adjusted Hazard Ratio (AHR): 0.90; 95% CI: 0.85, 0.95) and high quality indicator score (compared a low score, AHR: 0.43; 95% CI: 0.26, 0.73) had a protective effect on mortality. Patients with a high quality score were less likely to be lost to follow-up (Adjusted Odds Ratio (AOR): 0.42; 95% CI: 0.32, 0.56), compared to those with low score. These findings indicate that providing high quality care to children and adolescents living with HIV is important to improve outcomes, including lowering loss to follow-up and decreasing mortality in this age group

'Shooting in the dark': implications of the research-practice gap for enhancing research use in adult social care

Background: Despite calls for greater use of research and an appetite to do so within adult social care, a gap persists between research and practice. Aims and objectives: To explore views of adult social care staff about research and its application to everyday practice. To understand how these might impact upon research use capacity-building initiatives within adult social care organisations. Methods: Thematic analysis of semi-structured qualitative interviews with 25 staff members working within the adult social care departments of three English local authorities. Findings: Participants characterised research as feeling separate from practice. They reflected on their use of it in relation to pressures affecting adult social care and identified a lack of relevant research. Research benefiting service users, supporting individual practice or informing organisational decision-making was considered useful. However, research could also be viewed as a luxury where its findings were felt to represent an ‘ideal’ rather than real world of practice or did not accord with practice knowledge or local experience. Discussion and conclusions: While participants feel positively towards research, there remains a gap between these perceptions and its use in practice. There remains a need to improve research relevance and accessibility and to clarify its role in decision-making in social care, including where there is no evidence, where evidence challenges existing practice, or where the evidence base is growing. Collaborative partnerships between adult social care organisations, researchers and service users could help to narrow the research–practice gap and support the routine translation of research to practice

Zidovudine-based lytic-inducing chemotherapy for Epstein–Barr virus-related lymphomas

Treatment of Epstein–Barr virus (EBV)-related lymphomas with lytic-inducing agents is an attractive targeted approach for eliminating virus-infected tumor cells. Zidovudine (AZT) is an excellent substrate for EBV-thymidine kinase: it can induce EBV lytic gene expression and apoptosis in primary EBV+ lymphoma cell lines. We hypothesized that the combination of AZT with lytic-inducing chemotherapy agents would be effective in treating EBV+ lymphomas. We report a retrospective analysis of 19 patients with aggressive EBV+ non-Hodgkin lymphoma, including nine cases of acquired immune deficiency syndrome-associated primary central nervous system lymphoma (AIDSPCNSL) treated with AZT-based chemotherapy. Our results demonstrate that high-dose AZT–methotrexate is efficacious in treating highly aggressive systemic EBV+ lymphomas in the upfront setting. In primary EBV+ lymphoma cell lines, the combination of AZT with hydroxyurea resulted in synergistic EBV lytic induction and cell death. Further, AZT–hydroxyurea treatment resulted in dramatic responses in patients with AIDSPCNSL. The combination of AZT with chemotherapy, especially lytic-inducing agents, should be explored further in clinical trials for the treatment of EBV-related lymphomas

‘Shooting in the dark’: Implications of the research–practice gap for enhancing research use in adult social care

Background: Despite calls for greater use of research and an appetite to do so within adult social care, a gap persists between research and practice. Aims and objectives: To explore views of adult social care staff about research and its application to everyday practice. To understand how these might impact upon research use capacity-building initiatives within adult social care organisations. Methods: Thematic analysis of semi-structured qualitative interviews with 25 staff members working within the adult social care departments of three English local authorities. Findings: Participants characterised research as feeling separate from practice. They reflected on their use of it in relation to pressures affecting adult social care and identified a lack of relevant research. Research benefiting service users, supporting individual practice or informing organisational decision-making was considered useful. However, research could also be viewed as a luxury where its findings were felt to represent an ‘ideal’ rather than real world of practice or did not accord with practice knowledge or local experience. Discussion and conclusions: While participants feel positively towards research, there remains a gap between these perceptions and its use in practice. There remains a need to improve research relevance and accessibility and to clarify its role in decision-making in social care, including where there is no evidence, where evidence challenges existing practice, or where the evidence base is growing. Collaborative partnerships between adult social care organisations, researchers and service users could help to narrow the research–practice gap and support the routine translation of research to practice

hERG1a N-terminal eag domain–containing polypeptides regulate homomeric hERG1b and heteromeric hERG1a/hERG1b channels: A possible mechanism for long QT syndrome

Human ether-á-go-go–related gene (hERG) potassium channels are critical for cardiac action potential repolarization. Cardiac hERG channels comprise two primary isoforms: hERG1a, which has a regulatory N-terminal Per-Arnt-Sim (PAS) domain, and hERG1b, which does not. Isolated, PAS-containing hERG1a N-terminal regions (NTRs) directly regulate NTR-deleted hERG1a channels; however, it is unclear whether hERG1b isoforms contain sufficient machinery to support regulation by hERG1a NTRs. To test this, we constructed a series of PAS domain–containing hERG1a NTRs (encoding amino acids 1–181, 1–228, 1–319, and 1–365). The NTRs were also predicted to form from truncation mutations that were linked to type 2 long QT syndrome (LQTS), a cardiac arrhythmia disorder associated with mutations in the hERG gene. All of the hERG1a NTRs markedly regulated heteromeric hERG1a/hERG1b channels and homomeric hERG1b channels by decreasing the magnitude of the current–voltage relationship and slowing the kinetics of channel closing (deactivation). In contrast, NTRs did not measurably regulate hERG1a channels. A short NTR (encoding amino acids 1–135) composed primarily of the PAS domain was sufficient to regulate hERG1b. These results suggest that isolated hERG1a NTRs directly interact with hERG1b subunits. Our results demonstrate that deactivation is faster in hERG1a/hERG1b channels compared to hERG1a channels because of fewer PAS domains, not because of an inhibitory effect of the unique hERG1b NTR. A decrease in outward current density of hERG1a/hERG1b channels by hERG1a NTRs may be a mechanism for LQTS

Global benchmarks in primary robotic bariatric surgery redefine quality standards for Roux-en-Y gastric bypass and sleeve gastrectomy

BACKGROUND Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer

Printing bio-hybrid materials for bioelectronic cardio-3D-cellular constructs

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimise the mismatch between biological and electronic systems. We propose a strategy to bioprint bio-hybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multi-walled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibres. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behaviour of the hPSC-CMs and this effect is enhanced under the application of external ES. Genetic markers indicated a trend towards a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes

An international study to explore the feasibility of collecting standardised outcome data for Complex Regional Pain Syndrome: Recommendations for an international clinical research registry

Introduction: Complex Regional Pain Syndrome (CRPS) is a persistent pain condition with low prevalence. Multi-centre collaborative research is needed to attain sufficient sample sizes for meaningful studies. This international observational study: (1) tested the feasibility and acceptability of collecting outcome data using an agreed core measurement set (2) tested and refined an electronic data management system to collect and manage the data. Methods: Adults with CRPS, meeting the Budapest diagnostic clinical criteria, were recruited to the study from 7 international research centres. After informed consent, a questionnaire comprising the core set outcome measures was completed: on paper at baseline (T1), and at 3 or 6 months (T2) using a paper or e-version. Participants and clinicians provided feedback on the data collection process. Clinicians completed the CRPS severity score at T1 and optionally, at T2. Ethical approval was obtained at each international centre. Results: Ninety-eight adults were recruited (female n=66; mean age 46.6 years, range 19-89), of whom 32% chose to receive the T2 questionnaire in an electronic format. Fifty-five participants completed both T1 and T2. Eighteen participants and nine clinicians provided feedback on their data collection experience. Conclusion: This study confirmed the questionnaire core outcome data are feasible and practicable to collect in clinical practice. The electronic data management system provided a robust means of collecting and managing the data across an international population. The findings have informed the final data collection tools and processes which will comprise the first international, clinical research registry and data bank for CRPS

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema