Publications by authors named "Constantinos G Missouris"

69 Publications

Does Vitamin D have a role to play in Covid-19 in the dexamethasone era?

Diabetes Metab Syndr 2021 Jul 30;15(5):102237. Epub 2021 Jul 30.

University of Nicosia Medical School, Nicosia, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.dsx.2021.102237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321685PMC
July 2021

Dexamethasone treatment may mitigate adverse effects of vitamin D deficiency in hospitalized Covid-19 patients.

J Med Virol 2021 Jul 17. Epub 2021 Jul 17.

Department of Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

Aims: We have previously demonstrated that vitamin D deficiency might be associated with worse outcomes in hospitalized Covid-19 patients. The aim of our study was to explore this relationship with dexamethasone therapy.

Methods: We prospectively studied two cohorts of hospitalized Covid-19 patients between March and April and between September and December 2020 (n = 192). Patients were tested for serum 25-hydroxyvitamin D (25-OH-D) levels during admission. The first cohort not treated with dexamethasone (n = 107) was divided into vitamin D deficient (25-OH-D ≤ 30 nmol/L) (n = 47) and replete subgroups (25-OH-D > 30 nmol/L) (n = 60). The second cohort treated with dexamethasone (n = 85) was similarly divided into deficient (25-OH-D ≤ 30 nmol/L) (n = 27) and replete subgroups (25-OH-D > 30 nmol/L) (n = 58). Primary outcome was in-hospital mortality and secondary outcomes were elevation in markers of cytokine storm and ventilatory requirement.

Results: No mortality difference was identified between cohorts and subgroups. The "no dexamethasone" cohort 25-OH-D deplete subgroup recorded significantly higher peak D-Dimer levels (1874 vs. 1233 µgFEU/L) (p = 0.0309), CRP (177 vs. 107.5) (p = 0.0055), and ventilatory support requirement (25.5% vs. 6.67%) (p = 0.007) compared to the replete subgroup. Among the 25-OH-D deplete subgroup higher peak neutrophil counts, peak CRP, peak LDH, peak ferritin, and lower trough lymphocyte counts were observed, without statistical significance. In the "dexamethasone" cohort, there was no apparent association between 25-OH-D deficiency and markers of cytokine storm or ventilatory requirement.

Conclusion: Vitamin D deficiency is associated with elevated markers of cytokine storm and higher ventilatory requirements in hospitalized Covid-19 patients. Dexamethasone treatment appears to mitigate adverse effects of vitamin D deficiency.
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http://dx.doi.org/10.1002/jmv.27215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426812PMC
July 2021

Development, evaluation and validation of machine learning algorithms to detect atypical and asymptomatic presentations of Covid-19 in hospital practice.

QJM 2021 Jun 22. Epub 2021 Jun 22.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK.

Background: Diagnostic methods for Covid-19 have improved, both in speed and availability. Because of atypical and asymptomatic carriage of the virus and nosocomial spread within institutions, timely diagnosis remains a challenge. Machine learning models trained on blood test results have shown promise in identifying cases of Covid-19.

Aims: To train and validate a machine learning model capable of differentiating Covid-19 positive from negative patients using routine blood tests and assess the model's accuracy against atypical and asymptomatic presentations.

Design And Methods: We conducted a retrospective analysis of medical admissions to our institution during March and April 2020. Participants were categorised into Covid-19 positive or negative groups based on clinical, radiological features or nasopharyngeal swab. A machine learning model was trained on laboratory parameters and validated for accuracy, sensitivity and specificity and externally validated at an unconnected establishment.

Results: An Ensemble Bagged Tree model was trained on data collected from 405 patients (212 Covid-19 positive) producing accuracy of 81.79% (95% confidence interval (CI) 77.53% to 85.55%), sensitivity of 85.85% (CI 80.42% to 90.24%) and specificity of 76.65% (CI 69.49% to 82.84%). Accuracy was preserved for atypical and asymptomatic subgroups. Using an external data set for 226 patients (141 Covid-19 positive) accuracy of 76.82% (CI 70.87% to 82.08%), sensitivity of 78.38% (CI 70.87% to 84.72%) and specificity of 74.12% (CI 63.48% to 83.01%) was achieved.

Conclusion: A machine learning model using routine laboratory parameters can detect atypical and asymptomatic presentations of Covid-19, and might be an adjunct to existing screening measures.
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http://dx.doi.org/10.1093/qjmed/hcab172DOI Listing
June 2021

Elevated procalcitonin concentrations in severe Covid-19 may not reflect bacterial co-infection.

Ann Clin Biochem 2021 09 18;58(5):520-527. Epub 2021 Jun 18.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

Background: The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision-making. Procalcitonin is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between procalcitonin and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated.

Methods: We retrospectively reviewed Covid-19 patients with procalcitonin concentrations measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak procalcitonin values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality.

Results: In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak procalcitonin concentrations significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0,  = 0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6,  = 0.03). Higher peak procalcitonin concentrations was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4,  = 0.03). There was a significant positive correlation between increased peak procalcitonin concentrations and duration on invasive mechanical ventilation. No significant difference was found between peak procalcitonin concentrations of patients with positive and negative bacterial cultures.

Conclusions: Elevated procalcitonin concentrations in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.
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http://dx.doi.org/10.1177/00045632211022380DOI Listing
September 2021

COVID-19 encephalitis and Wernicke's encephalopathy.

J Med Virol 2021 Sep 24;93(9):5248-5251. Epub 2021 May 24.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK.

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http://dx.doi.org/10.1002/jmv.27088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242851PMC
September 2021

Covid-19, hypokalaemia and the renin-angiotensin-aldosterone system.

Ann Med Surg (Lond) 2021 May 27;65:102261. Epub 2021 Mar 27.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK.

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http://dx.doi.org/10.1016/j.amsu.2021.102261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003453PMC
May 2021

Drug-related bradycardia precipitating hospital admission in older adults: an ongoing problem.

Eur J Hosp Pharm 2021 Feb 24. Epub 2021 Feb 24.

Cardiology/Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

Background: Drug-related bradycardia (DRB) is a common clinical conundrum and can result in multiple hospital admissions as a result of the increased prescription of rate-limiting medications that can predispose to presyncopal or syncopal episodes.

Aim: To evaluate the incidence of DRB in elderly hospital inpatients.

Methods: We conducted a retrospective analysis of all patients admitted to our acute medical unit between November 2018 and February 2019 and identified patients over the age of 70 with more than one diurnal bradycardic episode during their admission. We extracted patient demographics, presenting complaint, admission 12-lead ECG and medications from the hospital electronic database.

Results: We screened 2312 adults and identified 100 patients over the age of 70 years with two or more episodes of diurnal bradycardia during their hospital admission. This constituted 4.32% of total admissions. Beta blockers were the most commonly prescribed rate-limiting medication (n=54, 87.1%), of which bisoprolol was the most frequently prescribed (n=41) and sinus bradycardia was the most commonly identified rhythm disturbance in our cohort of patients (n=41, 41%). Syncope was the most common presenting symptom and occurred in 23 patients, 14 (60.9%) of which were diagnosed with a DRB. Atrial fibrillation was more common in those with DRB compared with those with bradycardia not caused by medications (35.5% vs 10.5%, p=0.006), and atrial fibrillation was a significant predictor of DRB (OR=10.2, 95% CI 3.3 to 31.6, p<0.001).

Conclusion: Bradycardia is a significant cause of hospital admissions in older adults and can be avoided with pharmacovigilance. Caution should be exercised when initiating or changing the dose of rate-limiting agents in these patients; while those with atrial fibrillation should undergo regular review of their heart rate followed by appropriate medication dose adjustments.
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http://dx.doi.org/10.1136/ejhpharm-2020-002603DOI Listing
February 2021

Tachycardia and Bigeminy in a Patient With Shortness of Breath.

Ann Emerg Med 2021 02;77(2):260-263

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, Berkshire, UK; University of Cyprus Medical School, Nicosia, Cyprus.

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http://dx.doi.org/10.1016/j.annemergmed.2020.06.002DOI Listing
February 2021

COVID-19 in older adults: Typically atypical.

Geriatr Gerontol Int 2021 Jan 6;21(1):119-120. Epub 2020 Dec 6.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Frimley, UK.

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http://dx.doi.org/10.1111/ggi.14106DOI Listing
January 2021

Covid-19 and hypokalaemia - A potential mechanism.

Ann Clin Biochem 2021 05 1;58(3):259-260. Epub 2020 Dec 1.

Department of Cardiology and Internal Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

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http://dx.doi.org/10.1177/0004563220973497DOI Listing
May 2021

Donepezil induces ventricular arrhythmias by delayed repolarisation.

Naunyn Schmiedebergs Arch Pharmacol 2021 03 24;394(3):559-560. Epub 2020 Nov 24.

Department of Cardiology and Internal Medicine, Frimley Health NHS Foundation Trust, Wexham Park Hospital, Wexham Street, Slough, UK.

Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and I inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.
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http://dx.doi.org/10.1007/s00210-020-02028-4DOI Listing
March 2021

Prognostic implications of vitamin D in patients with COVID-19.

Eur J Nutr 2021 02;60(1):549-550

Departments of Cardiology and Internal Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK.

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http://dx.doi.org/10.1007/s00394-020-02429-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680660PMC
February 2021

In situ immune-mediated pulmonary artery thrombosis and Covid-19 pneumonitis.

Thromb Res 2021 01 11;197:112-113. Epub 2020 Nov 11.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK; University of Cyprus Medical School, Nicosia, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657098PMC
January 2021

Covid-19 and in situ pulmonary artery thrombosis.

Respir Med 2021 01 2;176:106176. Epub 2020 Oct 2.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK; University of Cyprus Medical School, Nicosia, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.rmed.2020.106176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529605PMC
January 2021

COVID-19 and late-onset hypertension with hyporeninaemic hypoaldosteronism.

Int J Clin Pract 2021 01;75(1):e13773

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

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http://dx.doi.org/10.1111/ijcp.13773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645887PMC
January 2021

Pulmonary embolism in COVID-19: Clinical characteristics and cardiac implications.

Am J Emerg Med 2020 Oct 24;38(10):2142-2146. Epub 2020 Jul 24.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK; University of Cyprus Medical School, Nicosia, Cyprus. Electronic address:

Background: The thrombogenic potential of Covid-19 is increasingly recognised. We aim to assess the characteristics of COVID-19 patients diagnosed with pulmonary embolism (PE).

Methods: We conducted a single centre, retrospective observational cohort study of COVID-19 patients admitted between 1st March and 30th April 2020 subsequently diagnosed with PE following computed tomography pulmonary angiogram (CTPA). Patient demographics, comorbidities, presenting complaints and inpatient investigations were recorded.

Results: We identified 15 COVID-19 patients diagnosed with PE (median age = 58 years [IQR = 23], 87% male). 2 died (13%), both male patients >70 years. Most common symptoms were dyspnoea (N = 10, 67%) and fever (N = 7, 47%). 12 (80%) reported 7 days or more of non-resolving symptoms prior to admission. 7 (47%) required continuous positive airway pressure (CPAP), 2 (13%) of which were subsequently intubated. All patients had significantly raised D-dimer levels, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and prothrombin times. The distribution of PEs correlated with the pattern of consolidation observed on CTPA in 9 (60%) patients; the majority being peripheral or subsegmental (N = 14, 93%) and only 1 central PE. 10 (67%) had an abnormal resting electrocardiogram (ECG), the commonest finding being sinus tachycardia. 6 (40%) who underwent transthoracic echocardiography (TTE) had structurally and functionally normal right hearts.

Conclusion: Our study suggests that patients who demonstrate acute deterioration, a protracted course of illness with non-resolving symptoms, worsening dyspnoea, persistent oxygen requirements or significantly raised D-dimer levels should be investigated for PE, particularly in the context of COVID-19 infection. TTE and to a lesser degree the ECG are unreliable predictors of PE within this context.
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http://dx.doi.org/10.1016/j.ajem.2020.07.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378013PMC
October 2020

Ibuprofen-Induced Distal Renal Tubular Acidosis and Hyporeninemic Hypoaldosteronism: Enough NSAID.

Mayo Clin Proc 2020 10;95(10):2296-2299

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK; University of Cyprus Medical School, Nicosia, Cyprus.

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http://dx.doi.org/10.1016/j.mayocp.2020.08.009DOI Listing
October 2020

Atypical presentation of COVID-19 in hospitalised older adults.

Ir J Med Sci 2021 May 21;190(2):469-474. Epub 2020 Sep 21.

Department of Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK.

Background: It is increasingly recognised that older patients may not present with typical symptoms of COVID-19.

Aims: This study aims to evaluate the incidence, characteristics and clinical outcome of older adults with atypical presentations of COVID-19.

Methods: A retrospective analysis of adults ≥ 65 years with confirmed COVID-19 admitted to our institution between 1 March and 24 April 2020 was performed. Patients were categorised into typical or atypical groups based on primary presenting complaint in the community.

Results: One hundred twenty-two patients (mean age 81 ± 8 years; 62 male) were included. Seventy-three (60%) were categorised into the typical group and 49 (40%) into the atypical group. In the atypical group, common presenting complaints were fall in 18 (36%), reduced mobility or generalised weakness in 18 (36%) and delirium in 11 (22%). Further assessment by paramedics and on admission found 32 (65%) to have typical features of COVID-19, fever being the most common, and 22 (44%) were hypoxic. This subset had worse outcomes than those in the typical group with a mortality rate of 50% versus 38%, respectively, although this was not statistically significant (P = 0.27). No significant difference in mortality or length of hospital stay between the groups was demonstrated.

Conclusion: Older patients with atypical presentation of COVID-19 in the community are equally susceptible to poor outcomes. Early detection may improve outcomes and limit community transmission. Primary care practitioners should be vigilant and consider prompt onward referral.
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http://dx.doi.org/10.1007/s11845-020-02372-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505490PMC
May 2021

Vitamin D status and COVID-19 in older adults.

Aging Clin Exp Res 2020 11 21;32(11):2425-2426. Epub 2020 Sep 21.

Departments of Cardiology and Internal Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK.

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http://dx.doi.org/10.1007/s40520-020-01716-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502654PMC
November 2020

Cause and duration of heart failure may impact on the response to sacubitril/valsartan in patients with heart failure and reduced ejection fraction.

J Cardiovasc Med (Hagerstown) 2021 03;22(3):233-234

Department of Cardiology, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

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http://dx.doi.org/10.2459/JCM.0000000000001111DOI Listing
March 2021

Vitamin D status and outcomes for hospitalised older patients with COVID-19.

Postgrad Med J 2021 Jul 27;97(1149):442-447. Epub 2020 Aug 27.

Department of Medicine, Frimley Health NHS Foundation Trust, Wexham Park Hospital, Slough, UK

Purpose: Older adults are more likely to be vitamin D deficient. The aim of the study was to determine whether these patients have worse outcomes with COVID-19.

Methods: We conducted a prospective cohort study between 1 March and 30 April 2020 to assess the importance of vitamin D deficiency in older patients with COVID-19. The cohort consisted of patients aged ≥65 years presenting with symptoms consistent with COVID-19 (n=105). All patients were tested for serum 25-hydroxyvitamin D (25(OH)D) levels during acute illness. Diagnosis of COVID-19 was confirmed via viral reverse transcriptase PCR swab or supporting radiological evidence. COVID-19-positive arm (n=70) was sub-divided into vitamin D-deficient (≤30 nmol/L) (n=39) and -replete groups (n=35). Subgroups were assessed for disease severity using biochemical, radiological and clinical markers. Primary outcome was in-hospital mortality. Secondary outcomes were laboratory features of cytokine storm, thoracic imaging changes and requirement of non-invasive ventilation (NIV).

Results: COVID-19-positive arm demonstrated lower median serum 25(OH)D level of 27 nmol/L (IQR=20-47 nmol/L) compared with COVID-19-negative arm, with median level of 52 nmol/L (IQR=31.5-71.5 nmol/L) (p value=0.0008). Among patients with vitamin D deficiency, there was higher peak D-dimer level (1914.00 μgFEU/L vs 1268.00 μgFEU/L) (p=0.034) and higher incidence of NIV support and high dependency unit admission (30.77% vs 9.68%) (p=0.042). No increased mortality was observed between groups.

Conclusion: Older adults with vitamin D deficiency and COVID-19 may demonstrate worse morbidity outcomes. Vitamin D status may be a useful prognosticator.
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http://dx.doi.org/10.1136/postgradmedj-2020-138712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456620PMC
July 2021

Letter to the Editor - New Pharmacotherapy for Heart Failure with Reduced Ejection Fraction.

Expert Rev Cardiovasc Ther 2020 09 1;18(9):651-652. Epub 2020 Aug 1.

Department of Cardiology, Wrexham Park Hospital, Frimley Health NHS Foundation Trust , Slough, UK.

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http://dx.doi.org/10.1080/14779072.2020.1799562DOI Listing
September 2020

Polymorphic cutaneous manifestations of COVID-19 infection in a single viral host.

Int J Dermatol 2020 Sep 19;59(9):1149-1150. Epub 2020 Jul 19.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

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http://dx.doi.org/10.1111/ijd.15072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405181PMC
September 2020

Comparison of the Effect of Sacubitril/Valsartan on Left Ventricular Systolic Function in Patients with Non-ischaemic and Ischaemic Cardiomyopathy.

Cardiovasc Drugs Ther 2020 12 9;34(6):755-762. Epub 2020 Jul 9.

Department of Cardiology, Wexham Park Hospital, Wexham Street, Slough, UK.

Purpose: Sacubitril/valsartan has been demonstrated to improve prognosis and outcomes in heart failure with reduced ejection fraction (HFrEF) patients. We sought to compare the improvement in cardiac function between non-ischaemic and ischaemic cardiomyopathy for patients receiving sacubitril/valsartan.

Methods: We conducted a single centre prospective cohort survey of patients reviewed in the Heart Function Clinic between February 2017 and January 2018. Functional evaluation and measurement of biochemical and echocardiographic parameters occurred before the initiation of sacubitril/valsartan, and after 3 months of treatment.

Results: We identified 52 patients (26 non-ischaemic and 26 ischaemic cardiomyopathy) suitable for treatment with sacubitril/valsartan. Treatment was followed by a significant decrease in a New York Heart Association (NYHA) class in both patients with non-ischaemic (2.3 ± 0.6 vs. 1.6 ± 0.7, P < 0.001) and ischaemic cardiomyopathy (2.3 ± 0.5 vs. 1.5 ± 0.6, P < 0.001), along with an increase in ejection fraction in both patients with non-ischaemic (26.2% ± 6.5% vs. 37.2% ± 13.8%, P < 0.001) and ischaemic cardiomyopathy (28.1% ± 5.7% vs. 31.5% ± 8.4%, P = 0.007). The improvement in ejection fraction was significantly greater in the patients with non-ischaemic cardiomyopathy compared to those with ischaemic cardiomyopathy (10.7% ± 13.0% vs. 3.9% ± 6.0%, P = 0.023).

Conclusion: Our study suggests that treatment with sacubitril/valsartan in patients with non-ischaemic cardiomyopathy is followed by a greater improvement in ejection fraction than in patients with ischaemic cardiomyopathy.
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http://dx.doi.org/10.1007/s10557-020-07036-3DOI Listing
December 2020

Pneumococcal coinfection in COVID-19 patients.

J Med Virol 2021 01 17;93(1):177-179. Epub 2020 Jul 17.

Department of Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

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http://dx.doi.org/10.1002/jmv.26278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361306PMC
January 2021

Long term use of donepezil and QTc prolongation.

Clin Toxicol (Phila) 2021 Mar 1;59(3):208-214. Epub 2020 Jul 1.

Department of Cardiology and Internal Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.

Background: The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear.

Objective: To investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval.

Methods: We conducted a single centre retrospective analysis of patients admitted to our trust on donepezil therapy over a 12-month period. An admission resting 12-lead ECG was obtained and compared to their ECG prior to commencement of donepezil therapy to assess for any significant difference in ECG parameters.

Results: We identified 59 patients suitable for analysis. PR (177.0 ± 29.0 ms vs. 186.1 ± 34.2 ms,  = 0.04), QRS (101.7 ± 20.3 ms vs. 104.7 ± 22.3 ms,  = 0.04) and QT (393.3 ± 35.6 ms vs. 411.9 ± 44.6 ms,  = 0.002) interval prolongation were all associated with donepezil use. The increase in QT intervals remained significant on correction for heart rate; resulting in 8 (13.6%) patients developing high arrhythmogenic risk based on assessment using QT nomogram plots. Concomitant use of tricyclic antidepressants was associated with significant QT prolongation (QTcB: = 0.344,  = 0.008, QTcFred: = 0.382,  = 0.003, QTcFram: = 0.379,  = 0.003, QTcH: = 0.352,  = 0.006), while the use of rate-limiting calcium channel blockers was associated with significant PR prolongation ( = 0.314,  = 0.030), and beta-blockers with a reduction in heart rate ( = 0.256,  = 0.050).

Conclusion: Our results clearly demonstrate that long-term use of donepezil is associated with prolongation of the QT interval. We suggest ECG evaluation should take place before and after donepezil initiation, and clinicians should be even more vigilant in those prescribed tricyclic antidepressants.
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http://dx.doi.org/10.1080/15563650.2020.1788054DOI Listing
March 2021

Sepsis Unmasking Fahr's Disease.

Am J Med Sci 2020 10 21;360(4):406-409. Epub 2020 May 21.

Wexham Park Hospital, Frimley Health NHS Foundation Trust, Berkshire, United Kingdom; University of Cyprus Medical School, Nicosia, Cyprus. Electronic address:

Fahr's disease is a sporadic or familial neurodegenerative disorder characterized by symmetrical calcification of cerebral structures, particularly the basal ganglia, cerebellar dentate nuclei and surrounding white matter, in the absence of metabolic causes of calcification. We report the case of a previously fit, high functioning 58-year-old man who developed catastrophic irreversible neuropsychiatric collapse after sepsis despite appropriate antimicrobial treatment. Cranial computed tomography revealed extensive diffuse calcifications located in unusual areas. Laboratory studies excluded the presence of other pathologic processes leading to secondary intracranial calcification and a multigene panel failed to confirm mutations in the genes currently known to be associated with the disorder, supporting a diagnosis of sporadic Fahr's disease or idiopathic brain calcification. Important diagnostic considerations in the septic patient who develops neurological complications, namely sepsis-associated encephalopathy and antibiotic-associated encephalopathy, are discussed. The patient remains severely handicapped 6 months after the acute event. Patients with clinically silent neurodegenerative/neuropsychiatric conditions, such as Fahr's disease, may present with florid and unpredicted neurological features in the context of systemic illness.
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http://dx.doi.org/10.1016/j.amjms.2020.05.023DOI Listing
October 2020
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