Management of pain in Fabry disease in the UK clinical setting: consensus findings from an expert Delphi panel.

BACKGROUND: Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting. METHODS: Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel's responses were conducted between September 2021 and December 2021. All questions required an answer. RESULTS: The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain. CONCLUSIONS: The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines.

Quality of Life with Late-Onset Pompe Disease: Qualitative Interviews and General Public Utility Estimation in the United Kingdom.

Background: Late-onset Pompe disease (LOPD) is a rare, progressive neuromuscular condition typically characterized by weakness of skeletal muscles, including those involved in respiration and diaphragmatic dysfunction. Individuals with LOPD typically eventually require mobility and/or ventilatory support. Objectives: This study aimed to develop health state vignettes and estimate health state utility values for LOPD in the United Kingdom. Methods: Vignettes were developed for 7 health states of LOPD with states defined in terms of mobility and/or ventilatory support. Vignettes were drafted based on patient-reported outcome data from the Phase 3 PROPEL trial (NCT03729362) and supplemented by a literature review. Qualitative interviews with individuals living with LOPD and clinical experts were conducted to explore the health-related quality-of-life (HRQoL) impact of LOPD and to review the draft vignettes. Vignettes were finalized following a second round of interviews with individuals living with LOPD and used in health state valuation exercises with people of the UK population. Participants rated the health states using the EQ-5D-5L, visual analogue scale, and time trade-off interviews. Results: Twelve individuals living with LOPD and 2 clinical experts were interviewed. Following the interviews, 4 new statements were added regarding dependence on others, bladder control problems, balance issues/fear of falling, and frustration. One hundred interviews with a representative UK population sample were completed. Mean time trade-off utilities ranged from 0.754 (SD = 0.31) (no support) to 0.132 (SD = 0.50) (invasive ventilatory and mobility support-dependent). Similarly, EQ-5D-5L utilities ranged from 0.608 (SD = 0.12) to -0.078 (SD = 0.22). Discussion: The utilities obtained in the study are consistent with utilities reported in the literature (0.670-0.853 for nonsupport state). The vignette content was based on robust quantitative and qualitative evidence and captured the main HRQoL impacts of LOPD. The general public rated the health states consistently lower with increasing disease progression. There was greater uncertainty around utility estimates for the severe states, suggesting that participants found it harder to rate them. Conclusion: This study provides utility estimates for LOPD that can be used in economic modeling of treatments for LOPD. Our findings highlight the high disease burden of LOPD and reinforce the societal value of slowing disease progression.

The Health Care Provider's Role in Securing Work Accommodations for Pregnant and Postpartum Patients.

Most women today are the primary, sole, or cobreadwinners for their families; their continued ability to work during and after pregnancy is crucial for their families' well-being. Midwives and other health care providers are regularly asked to provide work notes for patients who need adjustments to how, when, or where their job is done to continue working while maintaining a healthy pregnancy or breastfeeding. Whereas an improperly written work note can result in the patient being forced out on leave or losing their job, an effectively written work note from a health care provider can ensure the patient will receive the adjustments they need to stay safe and healthy on the job. Health care providers can also play an important role by incorporating discussions about workplace issues into care conversations. This article provides an overview of pregnancy-related employment rights, guidelines for writing effective work notes, and a discussion of common workplace issues patients face and how health care providers can respond.

Structural and functional measures of marine microbial communities: An experiment to assess implications for oil spill management.

Microbial communities are ecologically important in aquatic environments and impacts on microbes have the potential to affect a number of functional processes. We have amended seawater with a crude oil and assessed changes in species composition as well as a measure of functional diversity (the ability of the community to utilise different carbon sources) and the community level metabolic signature. We found that there was a degree of functional redundancy in the community we tested. Oiled assemblages became less diverse and more dominated by specialist hydrocarbon degraders, carbon source utilisation increased initially but there was no change in metabolic signature in this small scale laboratory experiment. This study supports the decision framework around management of oil spills. This package of methods has the potential to be used in the testing and selection of new dispersants for use in oil spill response.

Monitoring for a specific management objective: protection of shorebird foraging habitat adjacent to a waste water treatment plant.

Intertidal invertebrates are often used in environmental monitoring programs as they are good indicators of water quality and an important food source for many species of fish and birds. We present data from a monitoring program where the primary aim is to report on the condition of the potential invertebrate prey abundance, biomass and diversity for migrating shorebirds on mudflats adjacent to a waste water treatment plant in a Ramsar listed wetland in Victoria, Australia. A key threat to the foraging habitat at this site has been assessed as a reduction in potential prey items as a result of the changes to the waste water treatment processes. We use control charts, which summarise data from intertidal mudflats across the whole shoreline of the adjacent waste water treatment plant, to elicit a management response when trigger levels are reached. We then examine data from replicate discharge and control sites to determine the most appropriate management response. The monitoring program sits within an adaptive management framework where management decisions are reviewed and the data is examined at different scales to evaluate and modify our models of the likely outcomes of management actions. This study provides a demonstration of the process undertaken in a year when trigger levels were reached and a management decision was required. This highlights the importance of monitoring data from a range of scales in reducing uncertainty and improving decision making in complex systems.

Municipal wastewater effluent licensing: A global perspective and recommendations for best practice.

Advances in wastewater treatment have greatly improved the quality of municipal wastewater effluents in many parts of the world, but despite this, treated wastewaters can still pose a risk to the environment. Licensing plays a crucial role in the regulation of municipal wastewater effluents by setting standards or limits designed to protect the economic, environmental and societal values of waterbodies. Traditionally these standards have focused on physical and chemical water quality parameters within the discharge itself, however these approaches do not adequately account for emerging contaminants, potential effects of chemical mixtures, or variations in the sensitivity and resilience of receiving environments. In this review we focus on a number of industrialised countries and their approach to licensing. We consider how we can ensure licensing is effective, particularly when considering the rapid changes in our understanding of the impacts of discharges, the technical advances in our ability to detect chemicals at low concentrations and the progress in wastewater treatment technology. In order to meet the challenges required to protect the values of our waterways, licensing of effluents will need to ensure that there is no disconnect between the core values to be protected and the monitoring system designed to scrutinise performance of the WWTP. In many cases this may mean an expansion in the monitoring approaches used for both the effluent itself and the receiving waterbody.

Pregnant at work: time for prenatal care providers to act.

Fifty years ago, when a woman became pregnant, she was expected to stop working. Today, however, most women who work are the primary, sole, or co-breadwinner for their families, and their earnings during pregnancy are often essential to their families' economic well-being. Medical data about working during pregnancy are sparse but generally show that both low-risk and high-risk women can tolerate work-related duties well, although some work accommodations (eg, providing a chair for sitting, allowing snacks, or modifying the work schedule) may be necessary. However, some employers refuse to accommodate pregnant women who need adjustments. This can result in a woman being forced to make the choice between working without accommodations and losing her income and health insurance or even her job. Prenatal care providers can play an important role by implementing changes in their own practice, shaping public policy, and conducting research to increase protections for pregnant women and to ensure that they receive medically recommended accommodations while continuing to earn income for their growing families.