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Many paediatric studies report that patients must be established on aspirin therapy for a minimum of 5 days to achieve adequate response. This is not always practical especially in critical settings. Prospective identification of patients that are unresponsive to aspirin sooner could potentially prevent thrombotic events.
Aims:
The aim of this study was to investigate prospectively if the first dose of aspirin is effective in decreasing platelet aggregation, and thromboxane formation and if this can be measured after 2 hours in paediatric cardiology patients. A secondary aim was to identify a cut-off for a novel marker of aspirin responsiveness the maximum amplitude with arachidonic acid, which could potentially dramatically reduce the blood volume required. Third, we aimed to prospectively identify potentially non-responsive patients by spiking a sample of their blood ex vivo with aspirin.
Results:
The majority (92.3%) of patients were responsive, when measured 2 hours post first dose of aspirin. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. Additionally, we have shown a novel way to reduce blood sample volume requirements by measurement of the maximum amplitude with arachidonic acid as a marker of response, particularly for monitoring.
Conclusions:
These findings of rapid efficacy in the majority of patients offer assurance in a sound, practical way to attending clinicians, patients, and families.
Ischemic heart disease is the leading noninfectious cause of death in adults in the United States.
Acute coronary syndrome (ACS) refers to symptoms attributable to atherosclerotic disease of the epicardial coronary arteries, usually caused by a fixed atherosclerotic lesion of varying severity.
ACS is a spectrum of disease and can present as acute myocardial infarction (AMI) or unstable angina (UA). AMI is myocardial ischemia with necrosis and can occur with or without ST segment elevation. The latter is referred to as non-ST-segment elevation myocardial infarction (NSTEMI). UA is reversible myocardial ischemia without necrosis.
We previously analyzed five trials on ticagrelor/aspirin versus clopidogrel/aspirin in patients with minor stroke/ TIA in a network meta-analysis. We updated our search and identified 311 new citations with one study for inclusion: CHANCE2 enrolled patients with CYP2C19 loss-of-function alleles and randomized them to ticagrelor/aspirin or clopidogrel/aspirin. Pooling of CHANCE2 with the original studies could not be completed due to violation of NMA assumptions, due to significant inconsistency. This suggests patients with CYP2C19 loss-of-function alleles represent a subpopulation that is inherently different from the general stroke population in their antiplatelet response. Results from CHANCE-2 may not be generalizable without genotype testing.
This study aimed to discuss the role of large cavity functional endoscopic sinus surgery in the management of chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease.
Methods
This was a retrospective review of patients undergoing large cavity functional endoscopic sinus surgery for non-steroidal anti-inflammatory drug exacerbated respiratory disease from January 2016 to March 2022. Population characteristics, pre- and post-operative number of functional endoscopic sinus surgical procedures, endoscopic polyp grade, Lund–Mackay score and nasal symptoms were recorded.
Results
Thirteen consecutive patients with a median age of 47 years were included. They all failed maximal medical treatment and/or conservative functional endoscopic sinus surgery and underwent large cavity sinus surgery followed by post-operative maximal medical therapy. All patients showed an improvement in nasal symptoms with improved Lund–Mackay scores post-operatively. The median length of follow up was 1.5 years.
Conclusion
Large cavity functional endoscopic sinus surgery seems to halt the progression of chronic rhinosinusitis with nasal polyps in non-steroidal anti-inflammatory drug exacerbated respiratory disease. In this case series, large cavity functional endoscopic sinus surgery combined with optimal post-operative medical treatment appeared to switch off chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease.
Rhino-orbito-cerebral mucormycosis is a rapidly progressive disease with high mortality rates of about 60 per cent. The increasing incidence of rhino-orbito-cerebral mucormycosis in coronavirus disease 2019 patients in India and worldwide has become a matter of concern owing to the case fatality rate. This study explored the use of low dose aspirin in decreasing the mortality rate of coronavirus disease 2019 associated mucormycosis.
Method
This was a retrospective observational study. Patients suffering from post-coronavirus disease 2019 mucormycosis were included in the study. Each patient was treated with surgical debridement and systemic amphotericin B. Low dose aspirin was added, and mortality rates were compared with the patients who did not receive aspirin.
Results
The demographic data and rhino-orbito-cerebral mucormycosis staging between the two groups were not significantly different. There was a statistically significant difference in mortality outcomes between the two groups (p = 0.029) and a 1.77 times higher risk of dying for patients not receiving aspirin. Kaplan–Meier survival indicated that patients receiving aspirin had better survival rates (p = 0.04).
Long-term (>1 year) single antiplatelet therapy with aspirin is effective in reducing the risk of any early recurrent stroke by about one-sixth compared with no antiplatelet therapy. Clopidogrel monotherapy is marginally but significantly more effective than aspirin in reducing major vascular events. Cilostazol is also more effective than aspirin in Asian patients, and its therapeutic efficacy may be augmented by the addition of probucol in patients with ischaemic stroke and high risk of cerebral haemorrhage. The safety and effectiveness of cilostazol in non-Asian patients is not known. Prasugrel monotherapy (3.75 mg daily) is not non-inferior to clopidogrel monotherapy among Japanese patients with non-cardioembolic ischaemic stroke. Dual antiplatelet therapy with aspirin and extended-release dipyridamole is more effective than aspirin monotherapy and equally effective as clopidogrel monotherapy in preventing recurrent stroke. Dual antiplatelet therapy with aspirin and clopidogrel is more effective than aspirin monotherapy in preventing recurrent ischaemic stroke and myocardial infarction in high vascular risk patients, but it also increases the risk of major bleeding which may offset its benefits. Dual antiplatelet therapy with cilostazol added to aspirin or clopidogrel is more effective, and as safe as, aspirin or clopidogrel monotherapy in Japanese patients with non-cardioembolic ischaemic stroke.
Cervical artery dissection (CAD) is characterized by an intramural haematoma due to a subintimal tear and accounts for up to 25% of ischaemic strokes in young and middle-aged adults. Data regarding intravenous thrombolysis and endovascular thrombectomy in CAD are scarce and observational – both are reasonably safe and probably recommended. Based on observational evidence, antithrombotic therapy is used to prevent first or recurrent cerebral ischaaemic events in acute or subacute CAD, and event rates are low with either antiplatelet or anticoagulant therapy. The long-term rate of recurrent cerebral ischaemic events or bleeding complications in CAD patients is small while under antithrombotic treatment. Cerebral vasculitis treatment is based on observational series. When primary angiitis of the central nervous system is confirmed by biopsy, a combination of glucocorticoids and cyclophosphamide should be started. Rituximab may be used in patients who are intolerant of cyclophosphamide. In atypical, non-biopsy-proven cases, treatment should be adapted to the severity of neurological involvement. For giant cell arteritis, initial high-dose prednisolone is recommended, beginning a slow taper after 2–4 weeks and continuing at a low dose for 1–2 years. Treatment of p-ANCA-positive and -negative systemic vasculitis with cerebral involvement includes induction corticosteroid therapy followed by addition of cyclophosphamide or other glucocorticoid-sparing drugs.
Aspirin 160–300 mg daily started within 48 h of onset of acute ischaemic stroke is associated with a small beneficial reduction in recurrent ischaemic stroke (6 fewer per 1000 patients treated) and pulmonary embolism (1.5 fewer per 1000) that outweighs increased risk of bleeding (2 extra symptomatic ICHs and 4 extra major extracranial haemorrhages). The net effect is that, for every 1000 patients treated early with aspirin, 22 have reduced long-term disability, including 11 more achieving full recovery. Only two single antiplatelet regimens have been compared head to head against aspirin alone: cilostazol (a phosphodiesterase inhibitor) performed similarly to aspirin; ticagrelor (a GP IIa/IIIb receptor antagonist) showed tended to reduce ischaemic events but increased minor bleeding and dyspnea. In minor, non-cardioembolic ischaemic stroke or TIA, early dual antiplatelet therapy (DAPT) has shown advantages over early monotherapy. Most well-studied is clopidogrel and aspirin, with similar findings for dipyridamole and aspirin. DAPT reduces all-type (ischaemic and haemorrhagic) recurrent stroke (27 fewer per 1000 treated patients), but minimally increases major extracranial bleedings (3 more per 1000). Confining DAPT to the first 3 w maximizes the benefit to harm ratio. Anticoagulants alone and arterial-dose anticoagulants added to antiplatelet agents offer no net advantages over antiplatelet drugs alone. Venous prophylaxis-dose anticoagulants and aspirin, compared with aspirin alone, reduced recurrent ischaemic stroke more than it tend increased major extracranial haemorrhage.
Predictors of compliance with aspirin in children following cardiac catheterisation have not been identified. The aim of this study is to identify the caregivers’ knowledge, compliance with aspirin medication, and predictors of compliance with aspirin in children with Congenital Heart Disease (CHD) post-percutaneous transcatheter occlusion.
Methods:
A cross-sectional explorative design was adopted using a self-administered questionnaire and conducted between May 2017 and May 2018. Recruited were 220 caregivers of children with CHD post-percutaneous transcatheter occlusion. Questionnaires included child and caregivers’ characteristics, a self-designed and tested knowledge about aspirin scale (scoring scale 0–2), and the 8-item Morisky Medication Adherence Scale (scoring scale 0–8). Data were analysed using multivariate binary logistic regression analysis to identify predictors of compliance with aspirin.
Results:
Of the 220 eligible children and caregivers, 210 (95.5%) responded and 209 surveys were included in the analysis. The mean score of knowledge was 7.25 (standard deviation 2.27). The mean score of compliance was 5.65 (standard deviation 1.36). Child’s age, length of aspirin use, health insurance policies, relationship to child, monthly income, and knowledge about aspirin of caregivers were independent predictors of compliance with aspirin (p < 0.05).
Conclusion:
Caregivers of children with CHD had an adequate level of knowledge about aspirin. Compliance to aspirin medication reported by caregivers was low. Predictors of medium to high compliance with aspirin were related to the child’s age and socio-economic reasons. Further studies are needed to identify effective strategies to improve knowledge, compliance with medication, and long-term outcomes of children with CHD.
First do no harm’ is a fine principle; however, most medicines worth using have side effects, so it’s important that the prescriber can assess the risk/benefit ratio. This chapter provides examples of good advice (e.g. not to use NSAIDs in renal or liver impairment), overly cautious advice that may be flouted (e.g. cephalosporins in pencillin allergic patients) and advice that may appear overly cautious but should still be followed as there is a safer alternative (e.g.metformin in renal failure).
Mental, neurological and substance use disorders (MNS) constitute 13% of the global disease burden, surpassing both cardiovascular diseases and cancers. Major depressive disorder (MDD) and schizophrenia are among the three most disabling MNS illnesses worldwide. The contribution of chronic inflammation to major mental disorders has received increased attention in the last decade, which revealed a host of pharmacological targets. Multiple recent reviews clearly demonstrate that schizophrenia is associated with a dysregulation of immune responses, as reflected by the observed abnormal profiles of circulating pro- and anti-inflammatory cytokines in affected patients. Moreover, some anti-inflammatory drugs have shown their effectiveness in the treatment of schizophrenia. Anti-inflammatory drugs have shown effectiveness in major psychiatric disorders, especially major depressive disorder (MDD) and schizophrenia. Four major classes of anti-inflammatory drugs have been studied to date: polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. We discuss the positive results of PUFAs in MDD, the mixed results for COX-2 specific inhibitors and minocycline in schizophrenia, and the positive preliminary data on aspirin and n-acetyl-cysteine. Adjunctive aspirin was shown to significantly improve psychotic symptoms in schizophrenia, but only two randomized controlled trials were carried out to date. Anti-TNFalpha showed also important effectiveness in resistant MDD with blood inflammatory abnormalities, which may highlight potential biomarkers of interest. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD or schizophrenia. If used with caution, they may be reasonable therapeutic alternatives for resistant symptomatology.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
Methods
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
Results
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
Conclusions
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.
Method:
ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.
Results:
This paper presents the rationale for the study and presents a summary of the study design.
Conclusions:
ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
Samter's triad is a well described condition manifesting as chronic rhinosinusitis with nasal polyposis, asthma and aspirin intolerance in a non-atopic individual. The underlying mechanism is still to be fully elucidated. However, aural disease has not been widely reported in these patients. In the few reported cases, most patients underwent major surgery with varying degrees of success.
Case report:
We report two Samter's triad patients with aural involvement. Both were successfully managed by conservative treatment, thus avoiding the need for major surgery. It appears that more Samter's triad patients may have aural disease than previously thought.
Conclusion:
We report good outcomes with conservative treatment, which is relevant because aural disease tends to reoccur in these patients.
Tension-type headache (TTH) is the most common form of headache in the general population. The phenotypic features of TTH are non-specific and may be seen with an assortment of secondary headache conditions, which are linked mechanistically to an identifiable structural or physiological disorder. One recent study of psychiatric comorbidity in patients with migraine, TTH, and migraine plus TTH revealed significant differences in the rate of occurrence of depression, with the combined group being of highest risk. TTH is typically managed mainly through administration of medication during acute episodes. Simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and combination agents are most commonly recommended. Aspirin is more effective than placebo and comparable to the efficacy of acetaminophen in the relief of acute TTH. The prognosis is generally favorable, with limited disability during headache occurrences and age-related improvement or resolution of episodes later in life.
Shunt thrombosis after implantation of systemic-to-pulmonary shunts in paediatric patients is common. Acetyl salicylic acid is used for anti-thrombotic treatment; however, the effect is rarely monitored, although it is known that the response varies. The aim was to determine the effects of acetyl salicylic acid medication on platelet aggregation in children with systemic-to-pulmonary shunts.
Methods
A total of 14 children – median age 12 days; ranging from 3 to 100 days – were included in a prospective observational longitudinal study. All children were treated with oral acetyl salicylic acid (3–5 milligrams per kilogram once daily) after shunt implantation. Acetyl salicylic acid-dependent platelet aggregation in whole blood was analysed with impedance aggregometry (Multiplate®) after addition of arachidonic acid. Analyses were carried out before the primary operation, before and 5 and 24 hours after the first acetyl salicylic acid dose, and after 3–6 months of treatment. The therapeutic range for acetyl salicylic acid was defined as a test result less than 60 units.
Results
Acetyl salicylic acid reduced the arachidonic acid-induced platelet aggregation in all but one patient. Of the patients, 93% were in the therapeutic range 5 hours after acetyl salicylic acid intake, 86% were in the range after 24 hours, and 64% after 3–6 months.
Conclusions
Acetyl salicylic acid reduces platelet aggregation after shunt implantation in paediatric patients, but a considerable percentage of the children are outside the therapeutic range. Monitoring of platelet aggregation has the potential to improve anti-platelet treatment after shunt implantation by identifying children with impaired acetyl salicylic acid response.
Antiplatelet agents such as aspirin and clopidogrel are increasingly encountered in clinical practice. Otorhinolaryngological surgeons are involved in the peri-operative decision of whether to continue treatment and risk haemorrhage or to discontinue treatment and risk thrombosis.
Methods:
Literature relating to the risk of spontaneous or operative haemorrhage was reviewed. The morbidity and mortality associated with cessation of agents was evaluated. Published guidelines were also evaluated. A protocol for the management of antiplatelet agents in the peri-operative period, with particular reference to ENT operations, is presented.
Conclusion:
Significant morbidity and mortality is associated with the premature cessation of antiplatelet agents. Data from cardiac surgery suggest that operative blood loss only marginally increases in patients on aspirin and clopidogrel. However, the management of antiplatelet agents in the peri-operative period should be made after multidisciplinary consultation.
Clomiphene citrate (CC) and follicle stimulating hormone (FSH) are the two main modalities used for ovarian stimulation (OS). Decisions are based not only on randomized clinical trials (RCT), but also on other basic science and clinical evidence supporting their use. This chapter presents the effectiveness of adjuncts in enhancing outcomes in women having OS for in-vitro fertilization (IVF). The adjuncts include leuprolide acetate (LA) and gonadotropin-releasing hormone (GnRH) agonists, oral contraceptive (OC) pretreatment, estrogen pretreatment, dexamethasone (DEX), metformin (Met), human chorionic gonadotropin, aspirin (ASA), growth hormone (GH), dopamine agonists, and androgens and androgenic drugs. Most of these adjuncts are medications approved for other uses but not specifically as adjuncts for OS. The risk/benefit ratio in their use is quite favourable. Adjuncts aimed at improving ovarian response by increasing ovarian androgen concentrations appear to have real promise, but require further well-controlled studies to verify their effectiveness.
This chapter focuses on the primary antiphospholipid syndrome, that is, in the absence of systemic lupus erythematodes. Women with thrombophilia have an increased baseline risk of venous thromboembolism. In antiphospholipid syndrome, lupus anticoagulant is more strongly related to venous thrombosis and pregnancy complications than antibodies against phospholipids. The chapter reviews the evidence regarding potential clinical implications of acquired and inherited thrombophilia for both venous thromboembolism and for pregnancy failure. Treatment guidelines vary with regard to the administration of heparin for antiphospholipid syndrome and recurrent miscarriage. For women with antiphospholipid syndrome, the evidence regarding the efficacy of aspirin with or without the addition of low-molecular-weight heparin is not solid, whereas two small trials have shown a clear benefit of unfractionated heparin. For women with inherited thrombophilia, low-molecular-weight heparin to prevent pregnancy loss is definitely experimental as solid evidence is not yet available.
Venous thromboembolism (VTE) is the leading direct cause of maternal mortality in the UK, but many cases are potentially preventable. Risk factors for VTE should be identified pre-pregnancy, or at least early in pregnancy, and reassessed throughout pregnancy and the puerperium, as level of risk may change. Pregnancy itself is a risk factor for VTE, and additional risk factors include previous VTE, thrombophilia, and obesity. Thromboprophylaxis should be introduced depending on the level of risk. Guidelines are given for both ante-natal and post-natal management and in particular for the highest risk period immediately postpartum. Thromboprophylaxis involves both nonpharmacological and pharmacological measures, and the various modalities and drugs that can be used are discussed in this chapter. Non-pharmacological measures include appropriate hydration, early mobilization after surgery or delivery, graduated compression stockings (TEDS), and pneumatic compression boots. Aspirin, heparin, and warfarin are the main pharmacological agents to be used in thromboprophylaxis.