Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy.

Hypertension is a prevalent public health problem, contributing to >10 million deaths annually. Though multiple therapeutics exist, many patients suffer from treatment-resistant hypertension or try several medications before achieving blood pressure control. Genomic advances offer mechanistic understanding of blood pressure variability, therapeutic targets, therapeutic response, and promise a stratified approach to treatment of primary hypertension. Cyclic guanosine monophosphate augmentation, aldosterone synthase inhibitors, and angiotensinogen blockade with silencing RNA and antisense therapies are among the promising novel approaches. Pharmacogenomic studies have also been done to explore the genetic bases underpinning interindividual variability in response to existing therapeutics. A polygenic approach using risk scores is likely to be the next frontier in stratifying responses to existing therapeutics.

The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial.

COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear; one hypothesis is that loss of angiotensin-converting enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin-II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double-blind randomized, placebo-controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group; however, this did not reach statistical significance (P = .15). A Bayesian analysis demonstrated that there was a 92% probability that this change represented a true drug effect.

Selecting patients for interventional procedures to treat hypertension.

Purpose: Interventional approaches to treat hypertension are an emerging option that may be suitable for patients whose BP control cannot be achieved with lifestyle and/or pharmacotherapy and possibly for those who do not wish to take drug therapy.Materials and Methods: Interventional strategies include renal denervation with radiofrequency, ultrasound and alcohol-mediated platforms as well as baroreflex activation therapy and cardiac neuromodulation therapy. Presently renal denervation is the most advanced of the therapeutic options and is currently being commercialised in the EU.Results: It is apparent that RDN is effective in both unmedicated patients and patients with more severe hypertension including those with resistant hypertension.Conclusion: However, at present there is no evidence for the use of RDN in patients with secondary forms of hypertension and thus evaluation to rule these out is necessary before proceeding with a procedure. Furthermore, there are numerous pitfalls in the diagnosis and management of secondary hypertension which need to be taken into consideration. Finally, prior to performing an intervention it is appropriate to document presence/absence of hypertension-mediated organ damage.

RDN has emerged as a safe and effective approach to treat hypertension with BP lowering efficacy equivalent to antihypertensive monotherapy albeit with guaranteed 'adherence'Presently populations most likely to respond to RDN are not clearly defined but given the costs of the procedure it is likely to be initially made available to those with resistant hypertension and those at highest cardiovascular riskThere is no evidence to support the use of RDN in patients with secondary forms of hypertension and thus this should be thoroughly screened for prior to offering the procedure, especially in the setting of resistant hypertensionOptimisation of lifestyle and drug therapy is key to good hypertension management and should be undertaken prior to an invasive procedure such as RDN being offeredThere are numerous pitfalls in the screening process for secondary hypertension which means that hypertension specialists should be involved in this component of the pathwayRDN can be offered by interventional radiologist, interventional cardiologists or angiologists who have had appropriate trainingClinical pathways for RDN must ultimately involve a multidisciplinary team overview with hypertension specialists, interventionists and imaging specialists combining efforts to ensure appropriate patient selection. This without question must involve patients in the decision-making process.

Central arteriovenous anastomosis to treat resistant hypertension.

PURPOSE OF REVIEW: Novel, interventional treatments have emerged in the last decade for the treatment of resistant hypertension. This review focuses on a unique device that creates a fixed calibre, central iliac arteriovenous anastomosis that is significantly different in haemodynamic and safety profile from traditional haemodialysis fistulae. The background, physiology, and clinical data to date will be presented. RECENT FINDINGS: The single, randomized, controlled clinical trial using the ROX coupler in patients with resistant hypertension demonstrated substantial reductions in both office and ambulatory blood pressure to 12-month postimplantation. There was a common, but manageable, adverse effect of upstream iliac venous stenosis causing ipsilateral lower limb oedema. There were no renal safety concerns. The mechanism of action is proposed to be mechanical by provision of a low-pressure parallel circuit attached to the high-pressure arterial system though detailed physiological evaluation is currently lacking. SUMMARY: Preliminary data using the ROX coupler to form a central arteriovenous anastomosis are very encouraging. Concerns regarding the lack of sham control are to some extent mitigated by immediate on table blood pressure reduction with opening of the coupler and will be further addressed in the ongoing pivotal, sham-controlled ROX CONTROL Hypertension2 study which should provide further robust information regarding efficacy and safety.

A Discussion on the Regulation of Blood Flow and Pressure.

This paper discusses two kinds of regulation essential to the circulatory system: namely the regulation of blood flow and that of (systemic) arterial blood pressure. It is pointed out that blood flow requirements sub-serve the nutritional needs of the tissues, adequately catered for by keeping blood flow sufficient for the individual oxygen needs. Individual tissue oxygen requirements vary between tissue types, while highly specific for a given individual tissue. Hence, blood flows are distributed between multiple tissues, each with a specific optimum relationship between the rate of oxygen delivery (DO2) and oxygen consumption (VO2). Previous work has illustrated that the individual tissue blood flows are adjusted proportionately, where there are variations in metabolic rate and where arterial oxygen content (CaO2) varies. While arterial blood pressure is essential for the provision of a sufficient pressure gradient to drive blood flow, it is applicable throughout the arterial system at any one time. Furthermore, It is regulated independently of the input resistance to individual tissues (local arterioles), since they are regulated locally, that being the means by which the highly specific adequate local requirement for DO2 is ensured. Since total blood flow is the summation of all the individually regulated tissue blood flows cardiac inflow (venous return) amounts to total tissue blood flow and as the heart puts out what it receives cardiac output is therefore determined at the tissues. Hence, regulation of arterial blood pressure is independent of the distributed independent regulation of individual tissues. It is proposed here that mechanical features of arterial blood pressure regulation will depend rather on the balance between blood volume and venous wall tension, determinants of venous pressure. The potential for this explanation is treated in some detail.

Central iliac arteriovenous anastomosis for hypertension: targeting mechanical aspects of the circulation.

Raised blood pressure is the leading attributable risk factor for global morbidity and mortality. Real world data demonstrates that half of treated patients are at elevated cardiovascular risk because of inadequately controlled BP. In addition to pharmacotherapy, certain interventional strategies to reduce blood pressure and cardiovascular risk in hypertension can be considered according to international guidelines. One of the newer technologies entering this field is a proprietary arteriovenous coupler device that forms a fixed flow arteriovenous conduit in the central vasculature. In this review, we examine the development of and rationale for the creation of a central arteriovenous anastomosis in patients with hypertension and review the proposed mechanisms by which it may ameliorate hypertension. We critically review the clinical trial evidence base to date and postulate on future therapeutic directions.

Diagnosis and management of primary hyperaldosteronism in patients with hypertension: a practical approach endorsed by the British and Irish Hypertension Society.

Alongside the lack of homogeneity among international guidelines and consensus documents on primary hyperaldosteronism, the National UK guidelines on hypertension do not provide extensive recommendations regarding the diagnosis and management of this condition. Local guidelines vary from area to area, and this is reflected in the current clinical practice in the UK. In an attempt to provide support to the clinicians involved in the screening of subjects with hypertension and clinical management of suspected cases of primary hyperaldosteronism the following document has been prepared on the behalf of the BIHS Guidelines and Information Service Standing Committee. Through remote video conferences, the authors of this document reviewed an initial draft which was then circulated among the BIHS Executive members for feedback. A survey among members of the BIHS was carried out in 2022 to assess screening strategies and clinical management of primary hyperaldosteronism in the different regions of the UK. Feedback and results of the survey were then discussed and incorporated in the final document which was approved by the panel after consensus was achieved considering critical review of existing literature and expert opinions. Grading of recommendations was not performed in light of the limited available data from properly designed randomized controlled trials.

Adult hypertension referral pathway and therapeutic management: British and Irish Hypertension Society position statement.

In the UK, most adults with hypertension are managed in Primary Care. Referrals to Secondary Care Hypertension Specialists are targeted to patients in whom further investigations are likely to change management decisions. In this position statement the British and Irish Hypertension Society provide clinicians with a framework for referring patients to Hypertension Specialists. Additional therapeutic advice is provided to optimise patient management whilst awaiting specialist review. Our aim is to ensure that referral criteria to Hypertension Specialists are consistent across the UK and Ireland to ensure equitable access for all patients.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Non-pharmacological factors for hypertension management: a systematic review of international guidelines.

Lifestyle modifications are one of the cornerstones of hypertension prevention and treatment. We aimed to systematically review hypertension guidelines on their recommendations on non-pharmacological factors including lifestyle interventions, to highlight strength of evidence, similarities, and differences. This systematic review was registered with the international Prospective Register of Systematic Reviews (CRD42021288815). Publications in MEDLINE and EMBASE databases over 10 years since January 2010 to June 2020 were identified. We also included the search from websites of organizations responsible for guidelines development. Two reviewers screened the titles and abstracts to identify relevant guidelines. Two reviewers independently assessed rigour of guideline development using the AGREE II instrument, and one reviewer extracted recommendations. Of the identified guidelines, 10 showed good rigour of development (AGREE II ≥ 60%) and were included in the systematic review. The guidelines were consistent in most recommendations (reduced salt intake, weight, dietary patterns, increased physical activity and smoking cessation, and limiting alcohol intake). Some areas of disagreement were identified, regarding recommendations on novel psychological and environmental factors such as stress or air pollution, alcohol intake thresholds, meat, coffee and tea consumption and refined sugars. Current guidelines agree on the importance of lifestyle in the treatment and prevention of hypertension. Consensus on smoking cessation, limited salt intake, increased physical activity support their integration in management of hypertensive patients and in public health measurements in general population as preventative measurements. Further research into the role of environmental and psychological factors may help clarify future recommendations.

Improved lifestyle is associated with improved depression, anxiety and well-being over time in UK healthcare professionals during the COVID-19 pandemic: insights from the CoPE-HCP cohort study.

Background: One potential modifiable factor to improve the mental health of healthcare professionals (HCPs) during the pandemic is lifestyle. Aims: This study aimed to assess whether an improved lifestyle during the pandemic is associated with improved mental health symptoms and mental well-being in HCPs over time. Methods: This was a cohort study involving an online survey distributed at two separate time points during the pandemic (baseline (July-September 2020) and follow-up (December 2020-March 2021)) to HCPs working in primary or secondary care in the UK. Both surveys assessed for major depressive disorder (MDD) (Patient Health Questionnaire-9 (PHQ-9)), generalised anxiety disorder (GAD) (Generalised Anxiety Disorder-7 (GAD-7)), mental well-being (Short Warwick-Edinburgh Mental Well-being Score (SWEMWBS)) and self-reported lifestyle change (compared with the start of the pandemic) on multiple domains. Cumulative scores were calculated to estimate overall lifestyle change compared with that before the pandemic (at both baseline and follow-up). At each time point, separate logistic regression models were constructed to relate the lifestyle change score with the presence of MDD, GAD and low mental well-being. Linear regression models were also developed relating the change in lifestyle scores from baseline to follow-up to changes in PHQ-9, GAD-7 and SWEMWBS scores. Results: 613 HCPs completed both baseline assessment and follow-up assessment. Consistent significant cross-sectional associations between increased lifestyle change scores and a reduced risk of MDD, GAD and low mental well-being were observed at both baseline and follow-up. Over the study period, a whole unit increase in the change in novel scores (ie, improved overall lifestyle) over 4 months was inversely associated with changes in PHQ-9 (adjusted coefficient: -0.51, 95% confidence interval (CI): -0.73 to -0.30, p<0.001) and GAD-7 scores (adjusted coefficient: -0.32, 95% CI: -0.53 to -0.10, p=0.004) and positively associated with the change in SWEMWBS scores (adjusted coefficient: 0.37, 95% CI: 0.18 to 0.55, p<0.001). Conclusions: Improved lifestyle over time is associated with improved mental health and mental well-being in HCPs during the pandemic. Improving lifestyle could be a recommended intervention for HCPs to help mitigate the mental health impact during the current and future pandemics. Trial registration number: NCT04433260.

Management of hypertensive crisis: British and Irish Hypertension Society Position document.

Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.

Perceived workplace support and mental health, well-being and burnout among health care professionals during the COVID-19 pandemic: a cohort analysis.

BACKGROUND: Little is known about the relationship between workplace support and mental health and burnout among health care professionals (HCPs) during the COVID-19 pandemic. In this cohort study, we sought to evaluate the association between perceived level of (and changes to) workplace support and mental health and burnout among HCPs, and to identify what constitutes perceived effective workplace support. METHODS: Online surveys at baseline (July-September 2020) and follow-up 4 months later assessed the presence of generalized anxiety disorder (using the 7-item Generalized Anxiety Disorder scale [GAD-7]), clinical insomnia, major depressive disorder (using the 9-item Patient Health Questionnaire), burnout (emotional exhaustion and depersonalization) and mental well-being (using the Short Warwick-Edinburgh Mental Wellbeing Score). Both surveys assessed self-reported level of workplace support (single-item Likert scale). For baseline and follow-up, independently, we developed separate logistic regression models to evaluate the association of the level of workplace support (tricohotomized as unsupported, neither supported nor unsupported and supported) with mental health and burnout. We also developed linear regression models to evaluate the association between the change in perceived level of workplace support and the change in mental health scores from baseline and follow-up. We used thematic analyses on free-text entries of the baseline survey to evaluate what constitutes effective support. RESULTS: At baseline (n = 1422) and follow-up (n = 681), HCPs who felt supported had reduced risk of anxiety, depression, clinical insomnia, emotional exhaustion and depersonalization, compared with those who felt unsupported. Among those who responded to both surveys (n = 681), improved perceived level of workplace support over time was associated with significantly improved scores on measures of anxiety (adjusted ß -0.13, 95% confidence interval [CI] -0.25 to -0.01), depression (adjusted ß -0.17, 95% CI -0.29 to -0.04) and mental well-being (adjusted ß 0.19, 95% CI 0.10 to 0.29), independent of baseline level of support. We identified 5 themes constituting effective workplace support, namely concern or understanding for welfare, information, tangible qualities of the workplace, leadership and peer support. INTERPRETATION: We found a significant association between perceived level of (and changes in) workplace support and mental health and burnout of HCPs, and identified potential themes that constitute perceived workplace support. Collectively, these findings can inform changes in guidance and national policies to improve mental health and burnout among HCPs. Trial registration: ClinicalTrials.gov, no. NCT04433260.

A double-blind, randomised, placebo-controlled parallel study to investigate the effect of sex and dietary nitrate on COVID-19 vaccine-induced vascular dysfunction in healthy men and women: protocol of the DiNOVasc-COVID-19 study.

BACKGROUND: Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine. METHODS: DiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination. DISCUSSION: This study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central - Oxford C Research Ethics Committee (21/SC/0154).

Associations between radiographic findings and spirometry in a community exposed to Libby amphibole.

BACKGROUND: Among asbestos-exposed individuals, abnormal spirometry is usually associated with parenchymal abnormalities or diffuse pleural thickening. Localised pleural thickening (LPT), the most common abnormality associated with asbestos exposure, is typically thought to be a marker of exposure with little clinical consequence. Our objective was to determine if abnormal spirometry is associated with LPT independent of other abnormalities, using data from community-based screening conducted in Libby, Montana. METHODS: Subjects were a subset of screening participants comprising persons with interpretable spirometry and chest radiograph results (n=6475). Chest radiographs were independently evaluated by two or three B readers, and participants were classified by mutually exclusive categories of spirometry outcome: normal, restriction, obstruction or mixed defect. RESULTS: Restrictive spirometry was strongly associated with parenchymal abnormalities (OR 2.9; 95% CI 1.4 to 6.0) and diffuse pleural thickening (OR 4.1; 95% CI 2.1 to 7.8). Controlling for the presence of these abnormalities as well as age, smoking status and other covariates, restrictive spirometry was also associated with LPT (OR 1.4; 95% CI 1.1 to 1.8). The risk of restrictive spirometric findings correlated with the severity of LPT. CONCLUSIONS: In this large community-based screening cohort, restrictive spirometry is significantly associated with LPT, indicating that this abnormality may result in lung function impairment. Physicians treating patients exposed to Libby amphibole should be aware that LPT may have functional consequences.

Large cost savings realized from the 2006 Field Triage Guideline: reduction in overtriage in U.S. trauma centers.

BACKGROUND: Ambulance transport of injured patients to the most appropriate medical care facility is an important decision. Trauma centers are designed and staffed to treat severely injured patients and are increasingly burdened by cases involving less-serious injury. Yet, a cost evaluation of the Field Triage national guideline has never been performed. OBJECTIVES: To examine the potential cost savings associated with overtriage for the 1999 and 2006 versions of the Field Triage Guideline. METHODS: Data from the National Hospital Ambulatory Medical Care Survey and the National Trauma Databank (NTDB) produced estimates of injury-related ambulatory transports and exposure to the Field Triage guideline. Case costs were approximated using a cost distribution curve of all cases found in the NTDB. A two-way sensitivity analysis was also used to determine the impact of data uncertainty on medical costs and the reduction in trauma center visits (12%) after implementation of the 2006 Field Triage guideline compared with the 1999 Field Triage guideline. RESULTS: At a 40% overtriage rate, the average case cost was $16,434. The cost average of 44.2% reduction in case costs if patients were treated in a non-trauma center compared with a trauma center was found in the literature. Implementation of the 2006 Field Triage guideline produced a $7,264 cost savings per case, or an estimated annual national savings of $568,000,000. CONCLUSION: Application of the 2006 Field Triage guideline helps emergency medical services personnel manage overtriage in trauma centers, which could result in a significant national cost savings.

Quantifying the Excess Risk of Adverse COVID-19 Outcomes in Unvaccinated Individuals With Diabetes Mellitus, Hypertension, Ischaemic Heart Disease or Myocardial Injury: A Meta-Analysis.

Background: More than 80% of individuals in low and middle-income countries (LMICs) are unvaccinated against coronavirus disease 2019 (COVID-19). In contrast, the greatest burden of cardiovascular disease is seen in LMIC populations. Hypertension (HTN), diabetes mellitus (DM), ischaemic heart disease (IHD) and myocardial injury have been variably associated with adverse COVID-19 outcomes. A systematic comparison of their impact on specific COVID-19 outcomes is lacking. We quantified the impact of DM, HTN, IHD and myocardial injury on six adverse COVID-19 outcomes: death, acute respiratory distress syndrome (ARDS), invasive mechanical ventilation (IMV), admission to intensive care (ITUadm), acute kidney injury (AKI) and severe COVID-19 disease (SCov), in an unvaccinated population. Methodology: We included studies published between 1st December 2019 and 16th July 2020 with extractable data on patients ≥18 years of age with suspected or confirmed SARS-CoV-2 infection. Odds ratios (OR) for the association between DM, HTN, IHD and myocardial injury with each of six COVID-19 outcomes were measured. Results: We included 110 studies comprising 48,809 COVID-19 patients. Myocardial injury had the strongest association for all six adverse COVID-19 outcomes [death: OR 8.85 95% CI (8.08-9.68), ARDS: 5.70 (4.48-7.24), IMV: 3.42 (2.92-4.01), ITUadm: 4.85 (3.94-6.05), AKI: 10.49 (6.55-16.78), SCov: 5.10 (4.26-6.05)]. HTN and DM were also significantly associated with death, ARDS, ITUadm, AKI and SCov. There was substantial heterogeneity in the results, partly explained by differences in age, gender, geographical region and recruitment period. Conclusion: COVID-19 patients with myocardial injury are at substantially greater risk of death, severe disease and other adverse outcomes. Weaker, yet significant associations are present in patients with HTN, DM and IHD. Quantifying these associations is important for risk stratification, resource allocation and urgency in vaccinating these populations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, registration no: CRD42020201435 and CRD42020201443.

A cluster of tetrodotoxin poisoning in Oman.

INTRODUCTION: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. The severity of toxicity depends on the amount of toxin ingested and the outcome depends on the time-lapse to appropriate medical care. CASES REPORT: We report five patients who presented with tetrodotoxin poisoning after consuming fried internal organs of local pufferfish from the coast of Oman. The patients' clinical manifestations were consistent with the expected TTX toxidrome of perioral and generalized paresthesia, weakness of upper and lower extremities, gastrointestinal manifestations, dyspnea, dysarthria, ascending paralysis, hypotension, bradycardia and coma. The severity varied among the patients who recovered completely except one patient who developed a subarachnoid hemorrhage without underlying aneurysms on computed tomography-angiogram. This complication was potentially related to TTX poisoning and has not been previously reported. In addition to standard supportive management, patients with severe illness should potentially receive the intravenous acetylcholinesterase inhibitor neostigmine, and intermittent dialysis. Urine specimens were sent to CDC in Atlanta, where they were analyzed using online solid phase extraction (SPE) with LC-MS/MS and confirmed the diagnosis in all five cases. DISCUSSION: In general, the patients' clinical manifestations were consistent with the expected TTX toxidrome except patient 3 who developed a subarachnoid hemorrhage early during his clinical course. Two patients received neostigmine and underwent dialysis with complete recovery.

Longitudinal comparisons of mental health, burnout and well-being in patient-facing, non-patient-facing healthcare professionals and non-healthcare professionals during the COVID-19 pandemic: findings from the CoPE-HCP study.

BACKGROUND: The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs. AIMS: To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs. METHOD: Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase. RESULTS: A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15-5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40-7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12-9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65-15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28-5.85, P = 0.009) by phase 3. CONCLUSIONS: The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.