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Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.
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Background/Aims Rheumatic and musculoskeletal diseases (RMDs) are some of the most common indications for prescribed opioids. It is unclear how opioid prescribing has changed in the UK for RMDs, especially during the COVID-19 pandemic with limited healthcare access and cancelled elective-surgical interventions, which could impact prescribing in either direction. We aimed to investigate trends in opioid prescribing in RMDs and assess the impact of the pandemic in the UK. Methods Adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), systemic lupus erythematosus (SLE), osteoarthritis (OA) and fibromyalgia with opioid prescriptions between 01/Jan/2006-31/Aug/2021 without prior cancer in the UK Clinical Practice Research Datalink (CPRD) were included. We calculated ageand gender-standardised yearly rates of people with opioid prescriptions between 2006-2021, and identified change points in trends by checking whether the rate of change of standardised rates crossed zero. For people with opioid prescriptions, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006-2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of people with opioid prescriptions between Jan/2015-Aug/2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results We included 1,313,519 patients: 36,932 with RA, 12,649 with PsA, 6,811 with AxSpA, 6,423 with SLE, 1,255,999 with OA, and 66,944 with fibromyalgia. People with opioid prescriptions increased from 2006 to 2018 for OA, to 2019 for RA, AxSpA and SLE, to 2020 for PsA, and to 2021 for fibromyalgia, and all plateaued/decreased afterwards. OA patients on opioids increased from 466.8/10,000 persons in 2006 to a peak of 703.0 in 2018, followed by a decline to 575.3 in 2021. From 2006 to 2021, there was a 4.5-fold increase in fibromyalgia opioid users (17.7 vs.78.5/10,000 persons). In this period, MME/day increased for all RMDs, with the highest for fibromyalgia (>=35). During COVID-19 lockdowns, RA, PsA and fibromyalgia showed significant changes in the trend of people with opioid prescriptions. With a decreasing trend for RA (-0.001,95%CI=-0.002,-0.001) and a decreasing-to-flat curve for PsA (0.0010,95%CI=0.0006,0.0015) prepandemic until Feb/2020, the trends changed by -0.005 (95%CI=-0.008,-0.002) for RA and -0.003 (95%CI=-0.006,-0.0003) for PsA, leading to steeper decreasing trends during the pandemic (Mar/2020-Aug/2021). Fibromyalgia, conversely, had an increasing trend (0.009,95%CI=0.008,0.009) pre-pandemic, and this trend started decreasing by -0.009 (95%CI=-0.011,-0.006) during the pandemic. Conclusion The plateauing/decreasing trend of people with opioid prescriptions in RMDs after 2018 may reflect the efforts to tackle the rising opioid prescribing in UK primary care. Of all RMDs, fibromyalgia patients had the highest MME/day throughout the study period. COVID-19 lockdowns contribute to fewer people on opioids for most RMDs, reassuring there was no sudden increase in opioid prescribing during the pandemic.
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Coronavirus disease 2019 (COVID-19) causes significant mortality and morbidity, with an unknown impact in the medium to long term. Evidence from previous coronavirus epidemics indicates that there is likely to be a substantial burden of disease, potentially even in those with a mild acute illness. The clinical and occupational effects of COVID-19 are likely to impact on the operational effectiveness of the Armed Forces. Collaboration between Defence Primary Healthcare, Defence Secondary Healthcare, Defence Rehabilitation and Defence Occupational Medicine resulted in the Defence Medical Rehabilitation Centre COVID-19 Recovery Service (DCRS). This integrated clinical and occupational pathway uses cardiopulmonary assessment as a cornerstone to identify, diagnose and manage post-COVID-19 pathology.
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Objective: Non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding is a novel intervention for infants with feeding delays that may improve feeding and help avoid a gastrostomy tube (Gtube). However, the long-term impact of this neurostimulation on infant's development remains unknown. We investigated the neurodevelopmental and sensory outcomes of infants who received taVNS paired with bottle feeding. Method(s): Twenty-one of 35 toddlers who participated in the open label trial of taVNS paired with one or two feeds a day for 2-3 weeks, underwent comprehensive developmental assessments at 18 months of age using Cognitive Adaptive Test, Clinical Linguistics and Auditory Milestone, and Peabody gross motor scores. Twelve of those assessed achieved full oral feeds ('responders') and 9 had G-tube placed for feeds ('non-responders'). Before COVID, 12 toddlers (5 responders, 7 non-responders) were also assessed in the home using the Bayley-III and Sensory Profile (SP-2) assessments. Area deprivation index (ADI) was used to measure resource poor environments and relate to test scores. We used Fishers exact test and Pearson correlation coefficients to compare neurodevelopmental and sensory performance in responders versus non-responders. Result(s): taVNS responders showed significantly better general sensory processing in SP-2 than did non-responders (p =0.04). There were no significant differences in Bayley-III or CAT/CLAMS/ASQ scores in areas of cognition, receptive language, fine motor, and gross motor skills in this small sample size, but are similar to published scores for preterm infants who received G-tubes. ADI was not significantly associated with neurodevelopmental scores. Conclusion(s): These results suggest that taVNS paired with feeding may have a potential long-term positive neurodevelopmental effect on sensory processing in neonates with poor feeding. The current open-label results need testing in randomized controlled trials of taVNS paired with oral feeding in developmentally delayed infants failing oral feeds. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Neurodevelopment, taVNS, feeding, developmental delaysCopyright © 2023
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Extreme disruptive scenarios such as pandemic lockdown force people to alter regular daily routines, impacting their energy consumption pattern. The implication of such a disruptive scenario for a more extended period on energy consumption is uncertain. This study aimed to investigate the impact of COVID-19 lockdown on residential electricity consumption in 100 houses from the southwestern UK. For the study, we analysed highly granular (1-minutely) electricity consumption data for April-September 2020 compared to the same months in 2019 for the same houses. Our study showed statistically significant differences during the lockdown period (the analysed six months) in energy demand. The minutely average electricity demand was 1.4-10% lower during April-September 2020 than in 2019. Our analysis showed that not all houses had similar type of changes during the lockdown. Some houses demonstrated a 38% increase in electricity demand, whereas some houses showed a 54% reduction during the lockdown period compared to 2019. Some houses showed significantly higher electricity use during the morning and afternoon than in 2019, which might be due to working and schooling from homes during the lockdown. © International Building Performance Simulation Association, 2022
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Symposium title: Addressing chronic pain and the opioid epidemic using auricular neuromodulation Symposium description: Our proposed symposium integrates a diverse group of scientist and clinician experts (Drs. Cunningham, Wilkes, Khodaparast, Badran) who have committed to exploring the anti-nociceptive and opioid sparing effects of auricular neuromodulation to progress toward non-opioid interventions for chronic pain and opioid use disorders. The demand for chronic pain therapies has increased at an unprecedented rate over the last several decades, contributing in part to a surge in prescription and illicit opioid demand. Countless patients were escalated to prolonged, high-dose opioid regimens over years of treatment. By 2014, 5.4% of U.S. adults were estimated to use prescription opioids on a long-term basis. As the harms of opioid proliferation became increasingly clear, a dramatic paradigm shift occurred in which these drugs are now perceived as more dangerous than beneficial for chronic pain. New clinical guidelines highlight the risks of high-dose regimens as well as the limited benefits, particularly insufficient analgesia and hyperalgesia, associated with long-term use. According to this new perspective, the preferred therapeutic modality for many patients is to safely taper, or even completely stop, using opioids. Transcutaneous auricular neurostimulation (tAN) is a novel therapeutic paradigm that includes stimulation of both the auricular branch of the vagus nerve and auriculotemporal nerve (branch of trigeminal). tAN therapy results in clinically significant reductions in opioid withdrawal symptoms associated with opioid detoxification and tapering. Either adjunctive vagal or trigeminal stimulation modulates pain transmission suggesting overlapping common effector pathways, possibly targeting the endogenous opioid system, which could lead to a synergistic therapeutic benefit for pain. This symposium will explore the scientific basis for this hypothesis across targeted and interconnected topics, including fundamental neuropharmacological mechanisms underlying pain and opioids, clinical challenges of tapering opioids, managing opioid withdrawal symptoms with tAN, and the prospects for tAN to deliver a safe alternative treatment option for pain disorders. The United States is experiencing an epidemic for prescription and non-prescription opioids, which have continued to rise since the 1990s. During 2015, approximately 2.1 million people were severely dependent on prescription opioids, and 513,000 on heroin. In 2020, the Centers for Disease Control reported 93,331 substance use overdose deaths. The continuing increase in opioid-related deaths from 2015 (18%) to 2020 (60%) is partly attributed to the mental health crisis during the Covid-19 pandemic. Aside from pain mitigation, individuals with opioid use disorder (OUD) may be motivated to continue drug-seeking by both the positive reinforcement of the euphoric effects of opioids and the negative reinforcement of opioid withdrawal symptoms due to cessation. Alternative approaches for OUD are a major priority for government agencies given the substantial impact on health, social, and economic welfare. Transcutaneous auricular neurostimulation (tAN) is a non-invasive form of vagus and trigeminal neuromodulation that was recently proven to be an efficacious non-pharmacologic based treatment for reducing opioid withdrawal symptoms. In 2021, tAN therapy received FDA clearance as an adjunctive treatment for opioid withdrawal symptoms in adults. tAN therapy was also proven safe and effective in reducing symptoms of neonatal opioid withdrawal syndrome (NOWS) in neonates. tAN as an adjuvant was safe, well-tolerated, while facilitating the successful rapid weaning of oral morphine and decreasing length of stay in the neonatal ICU. Based on these preliminary findings, tAN therapy is currently in two NIH-funded pivotal clinical trials to: 1) evaluate the long-term effects of tAN on opioid use relapse prevention and cravings in adults with OUD, and 2) determine f tAN therapy can reduce withdrawal symptoms and reduce morphine length of treatment for neonates with NOWS. Lastly, we will explore how tAN could be utilized as neuromodulatory approach for opioid sparing, and ultimately pain mitigation. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Vagus Nerve Stimulation, Opioid Use Disorder, Pain, NeurostimulationCopyright © 2023
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CASE: A 79-year-old active male presented during the first COVID-19 pandemic surgery moratorium with late Staphylococcus lugdunensis periprosthetic total hip arthroplasty infection. Due to the unprecedented circumstances, novel treatment of IV and oral antibiotic suppression was trialed without preceding surgical intervention. At latest follow-up, the patient has two-year revision-free survival with normalization of inflammatory markers and MRI findings, and resolution of clinical symptoms. CONCLUSION: We report a novel surgery-sparing treatment for periprosthetic hip infection. Judicious caution should be used in the application of similar therapies, as host and organism characteristics likely contributed substantially to the success of this case.
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Introduction: Pulmonary endarterectomy (PEA) is the recommended treatment for patients with operable chronic thromboembolic pulmonary hypertension (CTEPH). Reducing PVR pre-surgery may lower the surgical risk, but efficacy of drug treatment in operable CTEPH has not yet been proven and surgeons are concerned that dissection may be more difficult in pre-treated patients. Methodology: A randomised, double-blind, placebo controlled, multinational prospective study was performed in patients with operable CTEPH and PVR >800 dynes.sec.cm-5 at baseline (NCT03273257). Patients were randomised to Riociguat or placebo for 3 months prior to PEA. Primary endpoint was the change in PVR from baseline to before PEA. Secondary endpoints included perioperative findings and evaluation of the PEA specimen. Planned recruitment was 88 patients over 2 years. Result(s): The study was terminated early because of slow recruitment and the COVID-19 pandemic. At the time of study cessation, 14 patients were randomised (7 in each group) and 11 patients completed PEA surgery. At diagnosis, PVR was 944.0 dynes.sec.cm-5 in the Riociguat group and 1007.5 dynes.sec.cm-5 in the control group. -5 -5 The mean change in PVR prior to PEA was -28.4% for Riociguat and -6.9% for placebo (p=0.14). Completeness of surgical clearance was as expected in all patients. In the Riociguat group ease of dissection plane was rated as easier in 1, normal in 3 and more difficult in 2. In the control group, it was rated as easier in 1 and normal in 4. There were no surgical complications or post-operative deaths and no new safety signals. Conclusion(s): Due to the premature study discontinuation and the limited sample size, we are unable to determine the impact of bridging therapy on PEA outcomes.
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Introduction: People with diabetes are particularly at high risk of becoming seriously unwell after contracting covid-19 infection. We do not fully understand underlying factors contributing to such risk/their respective contributions to outcomes. Methods: This population-based study included people living in the Greater Manchester conurbation with a recorded diagnosis of type 1 diabetes and type 2 diabeetes +subsequent covid-19 infection. Each individual with type 1 diabetes (n = 862)/ type 2 diabetes (n = 13,225) was matched with 3 covid-19 infected non-diabetes controls. Results: For type 1 diabetes individuals, the hospital admission rate in the first 28 days after covid-19 positive test was 10%vs4.7% in age/gender-matched controls (relative risk [RR] 2.1). For type 2 diabetes individuals, the hospital admission rate in the first 28 days after a covid-19 positive test was 16.3%vs11.6% in age/gender-matched controls(RR 1.4). Average Townsend score was higher in type 2 diabetes (1.8) vs matched controls(0.4), with a higher proportion of type 2 diabetes people in the top 2 quintiles of greatest disadvantage(p < 0.001). Within the group of covid-19 infected type 1 diabetes affected individuals, factors influencing the likelihood of admission included;age/body mass index (BMI)/ hypertension/ HbA1c/low HDL-cholesterol/ lower estimated glomerular filtration rate(eGFR)/COPD/being of African/ mixed ethnicity. In covid-19 infected type 2 diabetes individuals, factors potentially related to a higher admission rate included;age/Townsend Index/co-morbidity with COPD/asthma and severe mental illness(SMI)+lower eGFR. Metformin prescription lowered the admission likelihood. Conclusion: In a UK population, we have confirmed significantly higher likelihood of admission in people with diabetes following covid-19 infection. Several factors mediate the increased likelihood of hospital admission including metformin. For type 2 diabetes, the majority of factors related to increased admission rate are common to the general population but more prevalent in type 2 diabetes.
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Introduction: In this study we set out to determine the relative likelihood of death following covid-19 infection in people with type 2 diabetes when compared to those without type 2 diabetes. Methods: Analysis of digital health record data was performed relating to people living in the Greater Manchester conurbation (population 2.82 million) who had a recorded diagnosis of type 2 diabetes and subsequent covid-19 confirmed infection. Each individual with type 2 diabetes (n = 13,807) was matched with three covid-19 infected non-diabetes controls (n = 39583). Results: For type 2 diabetes individuals, their mortality rate after a covid-19 positive test was 7.7% vs 6.0% in matched controls;the relative risk (RR) of death was 1.28. From univariate analysis performed within type 2 diabetes individuals, likelihood of death following covid-19 recorded infection was lower in people taking metformin, sodium glucose cotransporter-inhibitor 2(SGLT-2i) or glucagon-like peptide-1( GLP-1) agonist. A lower estimated glomerular filtration rate (eGFR) was associated with a higher mortality rate, as was hypertension history. Likelihood of death following covid-19 infection was also higher in those people with diagnosis of COPD/severe enduring mental illness, and in people taking aspirin/ clopidogrel/insulin. Smoking in people with type 2 diabetes significantly increased mortality rate. In combined analysis of type 2 diabetes patients/controls, multiple regression modelling indicated that factors independently relating to higher likelihood of death (accounting for 26% of variance) were: type 2 diabetes/age/ malegender/social deprivation (higher Townsend index). Conclusion: Following confirmed infection with covid- 19 a number of factors are associated with mortality in type 2 diabetes individuals. Prescription of metformin, SGLT-2is or GLP-1 agonists + non-smoking status associated with reduced risk of death for people with type 2 diabetes. Age/male sex/social disadvantage associated with an increased risk of death.
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Background/Aims Coronavirus Disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). International mass vaccination schemes are implemented to control the disease and reduce mortality. The data on serological immune response among rheumatology patients receiving immunosuppressive therapy following SARS-CoV-2 vaccines is very sparse. We present a case of a rheumatoid arthritis patient receiving rituximab (RTX) who developed fatal nosocomial COVID-19 infection despite receiving SARS-CoV-2 vaccine. Methods A 71-year-old Caucasian male with longstanding seropositive rheumatoid arthritis, interstitial lung disease with bullous emphysema, paraproteinemia, osteoporosis, anxiety, and depression. His treatment included hydroxychloroquine, sulfasalazine, oral prednisolone (2- 5 mg), and RTX every 6 months. He received his last cycle of RTX almost 8 weeks before vaccination. This gentleman received two doses of COVID-19 mRNA Vaccine (BioNTech-Pfizer) eleven weeks apart. Nine weeks after the second vaccination he was admitted with supraventricular tachycardia and heart failure. This admission coincided with a COVID-19 outbreak in the ward. Eight patients and one staff member tested (PCR) positive during regular ward screening. All patients were initially asymptomatic, and six of them were fully vaccinated. He was allowed to go home with advice to self-isolate for 10 days. Two days after discharge, he presented to the emergency department with shortness of breath, lethargy, and cough. The diagnosis was COVID-19 pneumonitis and pre-renal acute kidney injury. He received supplemental oxygen, dexamethasone, and intravenous co-amoxiclav. Unfortunately, he died from COVID-19 pneumonitis on his sixth day of admission. Our patient was the only one among the nine SARS-CoV-2 positive individuals who developed symptomatic disease. Results It is known that RTX along with other immune modulatory drugs reduce the response to some vaccines such as the seasonal flu vaccine, and it is expected that the same effect could be seen after COVID-19 vaccination. Octave study is evaluating immune responses in patients with a range of chronic rheumatic conditions on specific immunomodulatory and biologic treatments. This has shown the response to vaccine was dependent on the disease cohort, with 90% of those with RTX-treated antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis and 54% of those with inflammatory arthritis responding less well than the baseline for healthy subjects. There is no evidence to suggest how long after RTX a patient should delay vaccination with a COVID-19 vaccine, but published consensus suggests 4-8 weeks. Conclusion More studies are needed to assess the response to SARS-COV-2 vaccines among immunocompromised patients and the need for a third vaccine dose if antibodies level were low. The first approved monoclonal antibody treatment-Ronapreve for treating and preventing acute covid-19 in adults, is a promising drug for poor vaccine responders who develop COVID-19 infection. This case also highlights the importance of infection control within hospital setting.
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IntroductionPrevention of nosocomial transmission was a priority for NHS hospital teams during the SARS-COV-2 pandemic. However, infection control policies were developed in the face of uncertainty about duration of infectivity, routes of transmission, and safety of shared admission spaces. We retrospectively reviewed all hospital admissions to the University Hospitals of Leicester (UHL) respiratory department, which managed more than 30% of UHL patients with a diagnosis of COVID-19 between March 2020 and March 2021to determine the proportion of cases with laboratory evidence of healthcare associated infection (HCAI) and mortality within 28 days of PCR conversionMethodsThis was a retrospective cohort study performed using a bespoke database collating COVID-19 throat swab (TS) PCR results for UHL (COVTRACK). Nosocomial transmission was identified by demonstrating PCR conversions during admission and categorized into definite (conversion time > 14 days) or probable (conversion time 8–14 days). In depth records based analysis was undertaken for patients admitted to respiratory medicine (RM) and deceased within 28 days after conversion.ResultsOut of 10485 patients admitted to the Respiratory Department at UHL, 2054 (19.6%) were COVID-19 spell positive, including 57 with probable (41) or definite HCAI (16). 23 patients (7 with definite HCAI) died within 28 days of PCR conversion (0.22%, of total admitted, 1.1% of COVID19 positive), with 21 (91%) deaths in the 2nd wave. Compared with non-COVID admissions not acquiring nosocomial infection, HCAI was significantly associated with older age (mean difference (95%CI) 11.5 (7.5–15.5) years), length of stay (median LOS 18 Vs 1 day) and multiple ward occupancy (median 3 vs 1 ward);all analyses p<0.001.DiscussionOur analysis suggests HCAI with SARS-COV-2 contributed a very small fraction of COVID-19 related morbidity and mortality at our department and in the majority the trajectory of care was not changed. Despite the high numbers of highly infectious cases during the 1st and 2nd wave, we successfully implemented a suite of infection control measures that effectively mitigated risk. High throughput in admission areas, multiple ward moves, and prolonged hospital stay were significant risk factors associated with HCAI.
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BACKGROUND: The risk of transmission of SARS-CoV-2 from aerosols generated by medical procedures is a cause for concern. AIM: To evaluate the evidence for aerosol production and transmission of respiratory infection associated with procedures that involve airway suctioning or induce coughing/sneezing. METHODS: The review was informed by PRISMA guidelines. Searches were conducted in PubMed for studies published between January 1st, 2003 and October 6th, 2020. Included studies examined whether nasogastric tube insertion, lung function tests, nasendoscopy, dysphagia assessment, or suctioning for airway clearance result in aerosol generation or transmission of SARS-CoV-2, SARS-CoV, MERS, or influenza. Risk of bias assessment focused on robustness of measurement, control for confounding, and applicability to clinical practice. FINDINGS: Eighteen primary studies and two systematic reviews were included. Three epidemiological studies found no association between nasogastric tube insertion and acquisition of respiratory infections. One simulation study found low/very low production of aerosols associated with pulmonary lung function tests. Seven simulation studies of endoscopic sinus surgery suggested significant increases in aerosols but findings were inconsistent; two clinical studies found airborne particles associated with the use of microdebriders/drills. Some simulation studies did not use robust measures to detect particles and are difficult to equate to clinical conditions. CONCLUSION: There was an absence of evidence to suggest that the procedures included in the review were associated with an increased risk of transmission of respiratory infection. In order to better target precautions to mitigate risk, more research is required to determine the characteristics of medical procedures and patients that increase the risk of transmission of SARS-CoV-2.