Clinical Management of DMD-Associated Cardiomyopathy

Over the past decade, cardiomyopathy has become the leading cause of mortality among patients with Duchenne muscular dystrophy (DMD). The majority of DMD patients over the age of 18 experience some degree of cardiac involvement. The primary cardiac manifestations of DMD include progressive left ventricular (LV) wall stress leading to LV dilatation and wall thinning, and the development of cardiac fibrosis, all of which culminate in decreased LV contractility and reduced cardiac output. Mortality in these patients is predominantly related to pump failure and fatal arrhythmias leading to sudden cardiac death. While basic guidelines for the management of cardiomyopathy in DMD patients exist, these recommendations are by no means comprehensive, and this chapter aims to provide further insight into appropriate clinical diagnosis and management of DMD-associated cardiomyopathy. Notably, earlier and more frequent cardiac assessment and care can allow for better outcomes for these patients. Pharmacological treatments typically include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, beta-adrenergic receptor blockers, mineralocorticoid receptor antagonists, and corticosteroids. Non-pharmacological therapies include automated implantable cardioverter defibrillators and left ventricular assist devices, as well as in rare cases cardiac transplantation. Additionally, many emerging therapies show great promise for improving standards of care. These novel therapies, based primarily on applied gene therapy and genome editing, have great potential to significantly alter the DMD care landscape in the near future

A Biomechanical Comparison of Proportional Electromyography Control to Biological Torque Control Using a Powered Hip Exoskeleton

BackgroundDespite a large increase in robotic exoskeleton research, there are few studies that have examined human performance with different control strategies on the same exoskeleton device. Direct comparison studies are needed to determine how users respond to different types of control. The purpose of this study was to compare user performance using a robotic hip exoskeleton with two different controllers: a controller that targeted a biological hip torque profile and a proportional myoelectric controller.MethodsWe tested both control approaches on 10 able-bodied subjects using a pneumatically powered hip exoskeleton. The state machine controller targeted a biological hip torque profile. The myoelectric controller used electromyography (EMG) of lower limb muscles to produce a proportional control signal for the hip exoskeleton. Each subject performed two 30-min exoskeleton walking trials (1.0 m/s) using each controller and a 10-min trial with the exoskeleton unpowered. During each trial, we measured subjects’ metabolic cost of walking, lower limb EMG profiles, and joint kinematics and kinetics (torques and powers) using a force treadmill and motion capture.ResultsCompared to unassisted walking in the exoskeleton, myoelectric control significantly reduced metabolic cost by 13% (p = 0.005) and biological hip torque control reduced metabolic cost by 7% (p = 0.261). Subjects reduced muscle activity relative to the unpowered condition for a greater number of lower limb muscles using myoelectric control compared to the biological hip torque control. More subjects subjectively preferred the myoelectric controller to the biological hip torque control.ConclusionMyoelectric control had more advantages (metabolic cost and muscle activity reduction) compared to a controller that targeted a biological torque profile for walking with a robotic hip exoskeleton. However, these results were obtained with a single exoskeleton device with specific control configurations while level walking at a single speed. Further testing on different exoskeleton hardware and with more varied experimental protocols, such as testing over multiple types of terrain, is needed to fully elucidate the potential benefits of myoelectric control for exoskeleton technology

Risk factors of mortality in neonates with neonatal encephalopathy in a tertiary newborn care unit in Zimbabwe over a 12-month period

Neonatal encephalopathy (NE) accounts for ~23% of the 2.4 million annual global neonatal deaths. Approximately 99% of global neonatal deaths occur in low-resource settings, however, accurate data from these low-resource settings are scarce. We reviewed risk factors of neonatal mortality in neonates admitted with neonatal encephalopathy from a tertiary neonatal unit in Zimbabwe. A retrospective review of risk factors of short-term neonatal encephalopathy mortality was conducted at Sally Mugabe Central Hospital (SMCH) (November 2018 -October 2019). Data were gathered using a tablet-based data capture and quality improvement newborn care application (Neotree). Analyses were performed on data from all admitted neonates with a diagnosis of neonatal encephalopathy, incorporating maternal, intrapartum, and neonatal risk predictors of the primary outcome: mortality. 494/2894 neonates had neonatal encephalopathy on admission and were included. Of these, 94 died giving a neonatal encephalopathy-case fatality rate (CFR) of 190 per 1000 admitted neonates. Caesarean section (odds ratio (OR) 2.95(95% confidence interval (CI) 1.39-6.25), convulsions (OR 7.13 (1.41-36.1)), lethargy (OR 3.13 (1.24-7.91)), Thompson score "11-14" (OR 2.98 (1.08-8.22)) or "15-22" (OR 17.61 (1.74-178.0)) were significantly associated with neonatal death. No maternal risk factors were associated with mortality. Nearly 1 in 5 neonates diagnosed with neonatal encephalopathy died before discharge, similar to other low-resource settings but more than in typical high-resource centres. The Thompson score, a validated, sensitive and specific tool for diagnosing neonates with neonatal encephalopathy was an appropriate predictive clinical scoring system to identify at risk neonates in this setting. On univariable analysis time-period, specifically a period of staff shortages due to industrial action, had a significant impact on neonatal encephalopathy mortality. Emergency caesarean section was associated with increased mortality, suggesting perinatal care is likely to be a key moment for future interventions

Palliative opioid use, palliative sedation and euthanasia:reaffirming the distinction

From PubMed via Jisc Publications RouterHistory: received 2018-11-12, revised 2019-05-08, accepted 2019-05-12Publication status: aheadofprintWe read with interest the extended essay published from Riisfeldt and are encouraged by an empirical ethics article which attempts to ground theory and its claims in the real world. However, such attempts also have real-world consequences. We are concerned to read the paper's conclusion that clinical evidence weakens the distinction between euthanasia and normal palliative care prescribing. This is important. Globally, the most significant barrier to adequate symptom control in people with life-limiting illness is poor access to opioid analgesia. Opiophobia makes clinicians reluctant to prescribe and their patients reluctant to take opioids that might provide significant improvements in quality of life. We argue that the evidence base for the safety of opioid prescribing is broader than that presented, restricting the search to palliative care literature produces significant bias as safety experience and literature for opioids and sedatives exists in many fields. This is not acknowledged in the synthesis presented. By considering additional evidence, we reject the need for agnosticism and reaffirm that palliative opioid prescribing is safe. Second, palliative sedation in a clinical context is a poorly defined concept covering multiple interventions and treatment intentions. We detail these and show that continuous deep palliative sedation (CDPS) is a specific practice that remains controversial globally and is not considered routine practice. Rejecting agnosticism towards opioids and excluding CDPS from the definition of routine care allows the rejection of Riisfeldt's headline conclusion. On these grounds, we reaffirm the important distinction between palliative care prescribing and euthanasia in practice. [Abstract copyright: © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Spatial organisation of groundwater dynamics and streamflow response from different hydropedological units in a montane catchment

Funding was provided by the Leibniz Association (SAW-2012-IGB 4167) within the International Leibniz Graduate School: Aquatic boundaries and linkages- Aqualink. We would like to thank the NRI staff for their help during field work.Peer reviewedPostprin

Sekundärprävention der Nutzung von Kindesmissbrauchsabbildungen im Internet: ein internationaler Überblicksversuch [Secondary prevention of the use of online child sexual exploitation material: an initial overview of international efforts]

Prevention of the consumption of online child sexual exploitation material presents society with a host of new challenges and is a priority of the European Union (EU). Alongside the identification and prosecution of individuals who use child sexual exploitation material, there is a strong desire to prevent these offences before they occur. Due to the reports of exponential rises in detected child sexual exploitation material offending behaviour, an enhanced focus has been on secondary prevention efforts. Based on prevention and intervention models, this article briefly reviews some of the secondary prevention deterrence and psychosocial intervention efforts in Europe, with the aim to inform and support professionals in research, politics and service provision in German-speaking countries who wish to develop such approaches. The article initially discusses the European Commission’s current classification criteria to better understand and classify child sexual abuse and exploitation prevention programs. Approaches to preventative deterrence by law enforcement agencies are addressed, alongside the importance of cross-sectional collaboration with various stakeholders such as technology companies (e.g., Microsoft) and nongovernmental organisations (e.g., the International Hotline Operators of Europe). This is particularly focused on the situational prevention efforts and deterrence of at-risk populations. Furthermore, psychosocial intervention providers, such as the Lucy Faithfull Foundation, Stop it Now! Helpline, Project PARAPHILE, Kein Täter werden and other secondary prevention services in Germany, show the growth and diversity of work by existing prevention providers. The article concludes with a discussion of current challenges in the prevention of child sexual exploitation material

Gateway to offending behaviour: permission-giving thoughts of online users of child sexual exploitation material.

The endorsement of permission-giving thoughts, or so-called cognitive distortions, has been discussed as a contributing factor in sexually abusive behaviour. The current study set out to explore the thinking patterns of offenders who have used/downloaded child sexual exploitation material (CSEM), based on a survey of professionals. A thematic analysis elicited four overarching themes, namely the Perceived Nature of Children (perception of children portrayed in CSEM, as well as children in general), Non-sexual Engagement with CSEM (motivating factors that are not inherently sexual in nature), Denial of Harm (perception of the level of harm caused by CSEM), and Expression of a General Sexual Preference (general interest in deviant sexual behaviour). These themes aid to explore the differences and similarities between contact and non-contact offenders and to improve the understanding of the role of permission-giving thoughts in this offending. Results are discussed in terms of their theoretical significance and future implications

Software development process of Neotree - a data capture and decision support system to improve newborn healthcare in low-resource settings

The global priority of improving neonatal survival could be tackled through the universal implementation of cost-effective maternal and newborn health interventions. Despite 90% of neonatal deaths occurring in low-resource settings, very few evidence-based digital health interventions exist to assist healthcare professionals in clinical decision-making in these settings. To bridge this gap, Neotree was co-developed through an iterative, user-centered design approach in collaboration with healthcare professionals in the UK, Bangladesh, Malawi, and Zimbabwe. It addresses a broad range of neonatal clinical diagnoses and healthcare indicators as opposed to being limited to specific conditions and follows national and international guidelines for newborn care. This digital health intervention includes a mobile application (app) which is designed to be used by healthcare professionals at the bedside. The app enables real-time data capture and provides education in newborn care and clinical decision support via integrated clinical management algorithms. Comprehensive routine patient data are prospectively collected regarding each newborn, as well as maternal data and blood test results, which are used to inform clinical decision making at the bedside. Data dashboards provide healthcare professionals and hospital management a near real-time overview of patient statistics that can be used for healthcare quality improvement purposes. To enable this workflow, the Neotree web editor allows fine-grained customization of the mobile app. The data pipeline manages data flow from the app to secure databases and then to the dashboard. Implemented in three hospitals in two countries so far, Neotree has captured routine data and supported the care of over 21,000 babies and has been used by over 450 healthcare professionals. All code and documentation are open source, allowing adoption and adaptation by clinicians, researchers, and developers

Does Cataract Surgery Alleviate Poverty? Evidence from a Multi-Centre Intervention Study Conducted in Kenya, the Philippines and Bangladesh

BACKGROUND: Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. METHODOLOGY/PRINCIPAL FINDINGS: A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh:$16 vs $24 p = 0.004, Philippines:$24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh:$23 vs $23 p = 0.20, Philippines:$45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. CONCLUSIONS/SIGNIFICANCE: This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals

“Getting pregnant during COVID-19 was a big risk because getting help from the clinic was not easy”: COVID-19 experiences of women and healthcare providers in Harare, Zimbabwe

The COVID-19 pandemic and associated measures may have disrupted delivery of maternal and neonatal health services and reversed the progress made towards dual elimination of mother-to-child transmission of HIV and syphilis in Zimbabwe. This qualitative study explores the impact of the pandemic on the provision and uptake of prevention of mother-to-child transmission (PMTCT) services from the perspectives of women and maternal healthcare providers. Longitudinal in-depth interviews were conducted with 20 pregnant and breastfeeding women aged 20–39 years living with HIV and 20 healthcare workers in two maternity polyclinics in low-income suburbs of Harare, Zimbabwe. Semi-structured interviews were held after the second and third waves of COVID-19 in March and November 2021, respectively. Data were analysed using a modified grounded theory approach. While eight antenatal care contacts are recommended by Zimbabwe’s Ministry of Health and Child Care, women reported only being able to access two contacts. Although HIV testing, antiretroviral therapy (ART) refills and syphilis screening services were accessible at first contact, other services such as HIV-viral load monitoring and enhanced adherence counselling were not available for those on ART. Closure of clinics and shortened operating hours during the second COVID-19 wave resulted in more antenatal bookings occurring later during pregnancy and more home deliveries. Six of the 20 (33%) interviewed women reported giving birth at home, assisted by untrained traditional midwives as clinics were closed. Babies delivered at home missed ART prophylaxis and HIV testing at birth despite being HIV-exposed. Although women faced multiple challenges, they continued to attempt to access services after delivery. These findings underline the importance of investing in robust health systems that can respond to emergency situations to ensure continuity of essential HIV prevention, treatment, and care services