Synthesis of ß,ß-Disubstituted Styrenes via Trimethylsilyl Trifluoromethanesulfonate-Promoted Aldehyde-Aldehyde Aldol Coupling-Elimination.

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine, α,α-disubstituted aldehydes condense with electron-rich aromatic aldehydes to yield ß,ß-disubstituted styrenes. More electron-rich aromatic aldehydes react more rapidly and in higher yield. Preliminary results suggest that the reaction may proceed via the ionization and formal deformylation of an aldol intermediate.

The Effect of COVID-19 on 30-Day Mortality Rates Amongst Fragility Hip Fracture Patients.

Aim Fragility hip fracture patients have always been vulnerable to high rates of short term mortality, an issue that may have been exacerbated by the ongoing COVID-19 pandemic. To date, published data regarding Irish hip fracture patients in the era of COVID-19 is limited. This study aims to assess the effect of COVID-19 on 30-day mortality rates amongst a group of Irish hip fracture patients. Additionally, patient demographics, length of stay, admission haematological parameters, fracture type and surgical procedure will be assessed. Methods A multicentre, observational, retrospective study of hip fracture patients (n = 1,017) admitted to six Dublin teaching hospitals during the COVID-19 pandemic (4th February to 9th July 2020) was performed. For comparative purposes, equivalent data was retrospectively collected relating to hip fracture patients admitted to the same six teaching hospitals during the same time period in 2019. Results 481 patients were admitted during the specified timeframe in 2020, compared with 536 in 2019. The mean patient age was 77.6 years and 65.9% of patients were female. There was no statistically significant overall difference in 30-day mortality rates between the study and control groups, at 5.4% in 2020 and 4.3% in 2019 (p=0.338). There was an insignificant decrease in mean length of stay (17.85 days in 2020 vs. 18.82 days in 2019; p=0.106). Advancing age (p=0.021), male gender (p=0.019), low admission haemoglobin (p=0.024) and high admission white cell count (p=0.019) were all associated with increased 30-day mortality. Conclusion We found no significant difference in 30-day mortality rates amongst our cohort of hip fracture patients at the height of the COVID-19 pandemic in Ireland. Advancing age, male gender, anaemia at admission and leucocytosis at admission were associated with increased 30-day mortality. The continuation of COVID-19 related safety protocols in the treatment of hip fracture patients is essential in maintaining a safe hip fracture service.

Friedel-Crafts Addition of Indoles to Nitrones Promoted by Trimethylsilyl Trifluoromethanesulfonate.

N-Alkylindoles undergo Friedel-Crafts addition to aryl and secondary alkyl nitrones in the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine to produce 3-(1-(silyloxyamino)alkyl)indoles. Spontaneous conversion to bisindolyl(aryl)methanes, which is thermodynamically favored for nitrones derived from aromatic aldehydes, is suppressed under the reaction conditions. The silyloxyamino group can be deprotected with tetrabutylammonium fluoride to yield hydroxylamines.

Challenges and solutions to returning to clinical training after research: a multidisciplinary survey of integrated academic trainees in West Yorkshire, United Kingdom.

BACKGROUND: Time out of clinical training can impact medical trainees' skills, competence and confidence. Periods of Out of Programme for Research (OOPR) are often much longer than other approved mechanisms for time of out training. The aim of this survey study was to explore the challenges of returning to clinical training following OOPR, and determine potential solutions. METHODS: All current integrated academic training (IAT) doctors at the University of Leeds (United Kingdom) and previous IAT trainees undertaking OOPR in the local region (West Yorkshire, United Kingdom)(n = 53) were invited to complete a multidisciplinary survey. RESULTS: The survey was completed by 33 participants (62% response rate). The most relevant challenges identified were completing the thesis whilst transitioning back to clinical work, the rapid transition between full-time research and clinical practice, a diminished confidence in clinical abilities and isolation from colleagues. Potential solutions included dedicated funds allocated for the renewal of lapsed skills, adequate notice of the clinical rotation to which trainees return, informing clinical supervisors about the OOPR trainee returning to practice and a mandatory return to standard clinical days. CONCLUSIONS: Addressing these issues has the potential to improve the trainee experience and encourage future trainees to take time out of training for research activities.

Trial of remote continuous versus intermittent NEWS monitoring after major surgery (TRaCINg): a feasibility randomised controlled trial.

BACKGROUND: Despite medical advances, major surgery remains high risk with up to 44% of patients experiencing postoperative complications. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient's mobility. The aim of this study was to evaluate the feasibility, acceptability and clinical outcomes of continuous remote monitoring after major surgery. METHODS: The study was a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery were randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring was achieved using the SensiumVitals® wireless patch which is worn on the patient's chest and monitors heart rate, respiratory rate and temperature continuously, and alerts the nurse when there is deviation from pre-set physiological norms. Feasibility was assessed by evaluating recruitment rate, adherence to protocol and randomisation and the amount of missing data. Clinical outcomes included time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of hospital readmission within 30 days of discharge. RESULTS: One hundred and thirty-six patients were randomised between October 2018 and April 2019: 67 to the control group and 69 to the intervention group. Recruitment was completed prior to the 12 month target with a high rate of eligibility and consent. Missing data was limited only to questionnaire responses; no participants were lost to follow-up and only one participant was withdrawn due to loss of capacity. The number of patients classed as 'drop-out' due to design (8.1%) were less than anticipated, and there were no participants who crossed over into the alternative trial allocation group. Seventeen participants in the intervention group (28%) did not adhere to the monitoring protocol. No formal comparisons between arms was undertaken; however, participants had fewer unplanned critical care admissions (1 versus 5) and had a shorter average length of hospital stay (11.6 days (95% confidence interval 9.5-13.7 days) versus 16.2 days (95% confidence interval 11.3-21.2 days)) in the continuous vital signs monitoring group. The time taken to receive antibiotics in cases of sepsis was similar in both arms. A cost-utility analysis indicated that the remote monitoring system was cost-saving when compared to standard NEWS monitoring alone. CONCLUSIONS: It is feasible to perform a large-scale randomised controlled trial of continuous remote monitoring after major surgery. Progression to a definitive multicentre randomised controlled trial would be appropriate, taking consideration of factors, such as patient adherence, that might mask the potential benefit of additional monitoring. TRIAL REGISTRATION: ISRCTN registry with study ID ISRCTN16601772 . Registered 30 August 2017.

The Patient's Second Hip Fracture - One in Ten.

Introduction The number of fragility hip fractures (>60 years) are estimated to triple/quadruple by 2050. It is estimated that the prevalence of patient's contralateral hip fractures (HF2s) will increase also. Methods Single hospital, Retrospective review, 2013-2017, Radiograph review, n = 822. Results Management of patient's 2nd hip fractures accounted for 10.5% of all hip fracture surgeries. ~50% occurred within 3 years of the 1st hip fracture. There was no statistically significant difference in discharge destination, length-of-stay or mortality between the HF1 and HF2 cohorts. Discussion Patients with HF2s comprised a significant and stable proportion of all hip fractures treated. We advocate for the provision of a Fracture Liaison Service in each of the 16 hip fracture operating hospitals in Ireland to optimise the secondary prevention of hip fractures.

Remote wireless vital signs monitoring on the ward for early detection of deteriorating patients: A case series.

INTRODUCTION: Remote wireless monitoring is a new technology that allows the continuous recording of ward patients' vital signs, supporting nurses by measuring vital signs frequently and accurately. A case series is presented to illustrate how these systems might contribute to improved patient surveillance. METHODS AND RESULTS: Five hospitals in three European countries installed a remote wireless vital signs monitoring system on medical or surgical wards. Heart rate, respiratory rate and temperature were measured by the system every 2 min. Four cases of (paroxysmal) atrial fibrillation are presented, two cases of sepsis and one case each of pyrexia, cardiogenic pulmonary edema and pulmonary embolisms. All cases show that the remote monitoring system revealed the first signs of ventilatory and circulatory deterioration before a change in the trends of the respective values became obvious by manual vital signs measurement. DISCUSSION: This case series illustrates that a wireless remote vital signs monitoring system on medical and surgical wards has the potential to reduce time to detect deteriorating patients.

Pápulas hipopigmentadas en niña sana / Hypopigmented Papules in a Healthy Girl

No disponible

Hip Fracture and the Weekend Effect in an Irish Trauma Hospital

Aims We examined the relationship between the 1-year mortality (OYM) rate and (i) those admitted at the weekend, (ii) those who underwent surgery at the weekend and (iii) those admitted during the NCHD changeover months (January & July) for the management of hip fracture in Tallaght University Hospital (TUH). Methods Admissions to TUH (2013 - 2016) with hip fracture (> 60 years old) were retrospectively examined. Data from the Irish Deaths and Events Registry was analysed to identify death events at 1 year. Logistic regression analysis was performed with respect to OYM with the three variables above. Results 646 hip fracture patients were admitted (2013 ­ 2016). 178 (27.5%) were weekend admissions, 183 (28.4%) underwent weekend surgery and 93 patients (14.4%) were admitted during NCHD changeover months. There was no significant relationship between OYM and (i) weekend admission, (ii) weekend surgery or (iii) changeover admission in TUH. Conclusion This study offers the first examination of the weekend effect on fragility hip fractures and mortality in Irish patients and reports no significant weekend effect regarding 1-year mortality in this hip fracture cohort.

Research waste in surgical randomized controlled trials.

BACKGROUND: Research waste is a major challenge for evidence-based medicine. It implicates misused resources and increased risks for research participants. The aim of this study was to quantify constituent components of waste in surgical RCTs and explore targets for improvement. METHODS: ClinicalTrials.gov was searched for RCTs registered between January 2011 and December 2012 using the keyword 'surgery'. The primary outcome was research waste, defined as non-publication, inadequate reporting or presence of an avoidable design limitation. Serial systematic searches of PubMed and Scopus databases were performed to determine publication status. Adequacy of reporting was assessed using the CONSORT checklist. Avoidable design limitations were evaluated according to the presence of bias and/or the absence of a cited systematic review of the literature. RESULTS: Of 5617 registered RCTs, 304 met all eligibility criteria. Overall, 259 of 304 (85·2 per cent) demonstrated at least one feature of waste. Of these, 221 (72·7 per cent) were published in a peer-reviewed journal and 219 were accessible for full-text review. Only 73 of 131 (55·7 per cent) RCTs with a pharmacological intervention and 24 of 88 (27 per cent) with a non-pharmacological intervention were reported adequately, and 159 of 219 (72·6 per cent) demonstrated an avoidable design limitation. Multicentre (odds ratio 0·31, 95 per cent c.i. 0·11 to 0·88) and externally funded (OR 0·35, 0·15 to 0·82) RCTs were less associated with research waste. CONCLUSION: This study identified a considerable burden of research waste in surgical RCTs. Future initiatives should target improvements in single-centre, poorly supported RCTs.

ANTECEDENTES: El despilfarro en investigación es uno de los mayores retos para la medicina basada en la evidencia. Conlleva mala utilización de los recursos y aumento de los riesgos para los participantes en las investigaciones. El objetivo de este trabajo fue cuantificar los componentes que conforman este despilfarro en los ensayos aleatorizados y controlados (randomised controlled trials, RCTs) del ámbito quirúrgico y explorar los aspectos clave de mejora. MÉTODOS: Se realizó una búsqueda de los RCTs registrados en la base de datos ClinicalTrials.gov entre enero de 2011 y diciembre de 2012, utilizando la palabra clave cirugía. La variable primaria fue el despilfarro en investigación, definido como la no publicación, el informe inadecuado o la presencia de debilidades del diseño evitables. Para determinar el estado de las publicaciones, se realizaron búsquedas sistemáticas en las bases de datos PubMed y Scopus. La adecuación del informe se evaluó usando la lista de verificación CONSORT. Las debilidades del diseño evitables se evaluaron de acuerdo con la presencia de sesgo y/o la ausencia de citación en revisiones sistemáticas publicadas en la literatura. RESULTADOS: De los 5.617 RCTs registrados, 304 cumplieron con los criterios de elegibilidad. De ellos, 259/304 (85%) cumplieron al menos una de las características de despilfarro. De estos, 221 (73%) se publicaron en una revista con peer review y 219 eran accesibles a texto completo. Únicamente 73/131 (56%) RCTs con una intervención farmacológica y 24/88 (27%) con una intervención no farmacológica presentaban un informe adecuado, y 159/219 (73%) se demostró una debilidad del diseño evitable. Los RCTs multicéntricos (OR: 0,31; i.c. del 95%: 0,11 a 0,88) y con financiación externa (OR: 0,35; i.c. del 95%: 0,15 a 0,82) se asociaron con menos despilfarro de investigación. CONCLUSIÓN: Este estudio constató una carga considerable de despilfarro en investigación en los RCTs quirúrgicos. Se deberían promover iniciativas de mejora, especialmente dirigidas a los RCTs realizados en un solo centro y con menos financiación.

One-Pot Enol Silane Formation-Alkylation of Ketones with Propargyl Carboxylates Promoted by Trimethylsilyl Trifluoromethanesulfonate.

Ketones readily undergo conversion to enol silanes in the presence of a trialkylamine base and trimethylsilyl trifluoromethanesulfonate (TMSOTf) and add to propargyl cations to yield ß-alkynyl ketones. The propargyl cations are generated in the same reaction flask through the TMSOTf-promoted ionization of propargyl acetates or propargyl propionates. A range of enol silane precursors and propargyl carboxylates reacts efficiently (20 examples, up to 99% yield). Cyclization of a representative product in the presence of TMSOTf provided 61% yield of the trisubstituted furan.

Trial of Remote Continuous versus Intermittent NEWS monitoring after major surgery (TRaCINg): protocol for a feasibility randomised controlled trial.

BACKGROUND: Despite medical advances, major surgery remains high risk. Up to 44% of patients experience postoperative complications, which can have huge impacts for patients and the healthcare system. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient's mobility. The aim of this study is to evaluate the feasibility, acceptability and clinical impacts of continuous remote monitoring after major surgery. METHODS: The study is a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery will be invited to participate if they have the capacity to provided informed, written consent and do not have a cardiac pacemaker or an allergy to adhesives. Participants will be randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring will be achieved using the SensiumVitals® wireless patch which is worn on the patient's chest and monitors heart rate, respiratory rate and temperature continuously and alerts the nurse when there is deviation from pre-set physiological norms. Participants will be followed up throughout their hospital admission and for 30 days after discharge. Feasibility will be assessed by evaluating recruitment rate, adherence to protocol and randomisation, and the amount of missing data. The acceptability of the patch to nursing staff and patients will be assessed using questionnaires and interviews. Clinical outcomes will include time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of readmission within 30 days of discharge. DISCUSSION: Early detection and treatment of complications minimises the need for critical care, improves patient outcomes, and produces significant cost savings for the healthcare system. Remote continuous monitoring systems have the potential to allow earlier detection of complications, but evidence from the literature is mixed. Demonstrating significant benefit over intermittent monitoring to offset the practical and economic implications of continuous monitoring requires well-controlled studies in high-risk populations to demonstrate significant differences in clinical outcomes; this feasibility trial seeks to provide evidence of how best to conduct such a confirmatory trial. TRIAL REGISTRATION: This study is listed on the ISRCTN registry with study ID ISRCTN16601772.

The impact of continuous versus intermittent vital signs monitoring in hospitals: A systematic review and narrative synthesis.

BACKGROUND: Continuous vital signs monitoring on general hospital wards may allow earlier detection of patient deterioration and improve patient outcomes. This systematic review will assess if continuous monitoring is practical outside of the critical care setting, and whether it confers any clinical benefit to patients. METHODS: MEDLINE®, MEDLINE® In-Process, EMBASE, CINAHL and The Cochrane Library were searched for articles that evaluated the clinical or non-clinical outcomes of continuous vital signs monitoring in adults outside of the critical care setting. The protocol was registered with PROSPERO (CRD42017058098). FINDINGS: Twenty-four studies met the inclusion criteria and reported outcomes on a total of 40,274 patients and 59 ward staff in nine countries. The majority of studies showed benefits in terms of critical care use and length of hospital stay. Larger studies were more likely to demonstrate clinical benefit, particularly critical care use and length of hospital stay. Three studies showed cost-effectiveness. Barriers to implementation included nursing and patient satisfaction and the burden of false alerts. CONCLUSIONS: Continuous vital signs monitoring outside the critical care setting is feasible and may provide a benefit in terms of improved patient outcomes and cost efficiency. Large, well-controlled studies in high-risk populations are required to evaluate the clinical benefit of continuous monitoring systems.

Patient attitudes towards remote continuous vital signs monitoring on general surgery wards: An interview study.

BACKGROUND: Vital signs monitoring is used to identify deteriorating patients in hospital. The most common tool for vital signs monitoring is an early warning score, although emerging technologies allow for remote, continuous patient monitoring. A number of reviews have examined the impact of continuous monitoring on patient outcomes, but little is known about the patient experience. This study aims to discover what patients think of monitoring in hospital, with a particular emphasis on intermittent early warning scores versus remote continuous monitoring, in order to inform future implementations of continuous monitoring technology. METHODS: Semi-structured interviews were undertaken with 12 surgical inpatients as part of a study testing a remote continuous monitoring device. All patients were monitored with both an early warning score and the new device. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. FINDINGS: Patients can see the value in remote, continuous monitoring, particularly overnight. However, patients appreciate the face-to-face aspect of early warning score monitoring as it allows for reassurance, social interaction, and gives them further opportunity to ask questions about their medical care. CONCLUSION: Early warning score systems are widely used to facilitate detection of the deteriorating patient. Continuous monitoring technologies may provide added reassurance. However, patients value personal contact with their healthcare professionals and remote monitoring should not replace this. We suggest that remote monitoring is best introduced in a phased manner, and initially as an adjunct to usual care, with careful consideration of the patient experience throughout.

Postoperative ileus following major colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is characterized by delayed gastrointestinal recovery following surgery. Current knowledge of pathophysiology, clinical interventions and methodological challenges was reviewed to inform modern practice and future research. METHODS: A systematic search of MEDLINE and Embase databases was performed using search terms related to ileus and colorectal surgery. All RCTs involving an intervention to prevent or reduce POI published between 1990 and 2016 were identified. Grey literature, non-full-text manuscripts, and reanalyses of previous RCTs were excluded. Eligible articles were assessed using the Cochrane tool for assessing risk of bias. RESULTS: Of 5614 studies screened, 86 eligible articles describing 88 RCTs were identified. Current knowledge of pathophysiology acknowledges neurogenic, inflammatory and pharmacological mechanisms, but much of the evidence arises from animal studies. The most common interventions tested were chewing gum (11 trials) and early enteral feeding (11), which are safe but of unclear benefit for actively reducing POI. Others, including thoracic epidural analgesia (8), systemic lidocaine (8) and peripheral µ antagonists (5), show benefit but require further investigation for safety and cost-effectiveness. CONCLUSION: POI is a common condition with no established definition, aetiology or treatment. According to current literature, minimally invasive surgery, protocol-driven recovery (including early feeding and opioid avoidance strategies) and measures to avoid major inflammatory events (such as anastomotic leak) offer the best chances of reducing POI.

The penalty points system in Ireland - Does it remain effective 14 years on?

INTRODUCTION: Road traffic accidents (RTAs) are the leading cause of trauma related mortality in Ireland. The penalty points system (PPS) was introduced in Ireland in 2002 to incentivise safer driving and reduce injury. Its early effect was studied previously1 which concluded that there was a slight reduction in RTA related femoral shaft fractures (a sensitive indicator of high energy trauma) and a dramatic reduction in RTA related discharges. We hypothesized that over the following 14 years, the penalty points system might lose its effectiveness. METHODS: Data was again collected from the same HIPE departments from six Dublin teaching hospitals and also University Hospital Waterford (to represent both an urban and a more rural population cohort respectively) examining RTA related femoral shaft fractures over an identical 6 month period (October-April). RTA related discharge data over an identical 6 month period was again acquired and analysed from Beaumont Hospital, Dublin (identical data source to previous study). These results were compared with the identical 6 month period in 2001/02 & 2002/03 (October-April). RESULTS: The total number of RTA related femoral shaft fracture discharges in Dublin decreased from 16 post introduction of PPS in the 2002/03 6-month period to 7 in 2015/16 6-month period. The number remained the same in the Waterford region (n = 5). The total RTA related discharges in Beaumont Hospital, Dublin decreased from 70 post PPS introduction to 57 in the 2015/16 6-month period. This represents an incidence rate of 4.5/1000 discharges (vs 6.9 post introduction) which was a statistically significant reduction (p = 0.014). The mean length of stay for these patients reduced from 13 to 7.7 days. There were consistent reductions in head injury (major & minor), lower limb fracture and facial fracture since the introduction of the PPS. The upper limb, pelvic/acetabular and thoracic injuries remained largely unchanged. Whilst RTA related spinal and abdominal injuries decreased after the introduction of the PPS, this study shows that these injuries have unfortunately increased since the post-PPS study in 2002/03. CONCLUSIONS: These results further support the effectiveness of the penalty points system and at a time where road death figures are under the spotlight, endorse the efficacious strategies implemented by the road safety authority in Ireland.

Strengths and limitations of early warning scores: A systematic review and narrative synthesis.

BACKGROUND: Early warning scores are widely used to identify deteriorating patients. Whilst their ability to predict clinical outcomes has been extensively reviewed, there has been no attempt to summarise the overall strengths and limitations of these scores for patients, staff and systems. This review aims to address this gap in the literature to guide improvements for the optimization of patient safety. METHODS: A systematic review was conducted of MEDLINE®, PubMed, CINAHL and The Cochrane Library in September 2016. The citations and reference lists of selected studies were reviewed for completeness. Studies were included if they evaluated vital signs monitoring in adult human subjects. Studies regarding the paediatric population were excluded, as were studies describing the development or validation of monitoring models. A narrative synthesis of qualitative, quantitative and mixed- methods studies was undertaken. FINDINGS: 232 studies met the inclusion criteria. Twelve themes were identified from synthesis of the data: Strengths of early warning scores included their prediction value, influence on clinical outcomes, cross-specialty application, international relevance, interaction with other variables, impact on communication and opportunity for automation. Limitations included their sensitivity, the need for practitioner engagement, the need for reaction to escalation and the need for clinical judgment, and the intermittent nature of recording. Early warning scores are known to have good predictive value for patient deterioration and have been shown to improve patient outcomes across a variety of specialties and international settings. This is partly due to their facilitation of communication between healthcare workers. There is evidence that the prediction value of generic early warning scores suffers in comparison to specialty-specific scores, and that their sensitivity can be improved by the addition of other variables. They are also prone to inaccurate recording and user error, which can be partly overcome by automation. CONCLUSIONS: Early warning scores provide the right language and environment for the timely escalation of patient care. They are limited by their intermittent and user-dependent nature, which can be partially overcome by automation and new continuous monitoring technologies, although clinical judgment remains paramount.

Friedel-Crafts Hydroxyalkylation of Indoles Mediated by Trimethylsilyl Trifluoromethanesulfonate.

Indoles and N-alkylindoles undergo Friedel-Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1-silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.

Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding.

BACKGROUND: A procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with a fatal outcome is unclear. OBJECTIVES: To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non-fatal CM. METHODS/PATIENTS: Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy-positive CM (n = 140), retinopathy-negative CM (n = 36), non-malarial coma (n = 14), uncomplicated malaria (UM), (n = 91), mild non-malarial febrile illness (n = 85), and healthy controls (n = 36). Assays in the ISTH DIC criteria were performed, and three fibrin-related markers, i.e. protein C, antithrombin, and soluble thrombomodulin, were measured. RESULTS AND CONCLUSIONS: Data enabling assignment of the presence or absence of 'overt DIC' were available for 98 of 140 children with retinopathy-positive CM. Overt DIC was present in 19 (19%), and was associated with a fatal outcome (odds ratio [OR] 3.068; 95% confidence interval [CI] 1.085-8.609; P = 0.035]. The levels of the three fibrin-related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all P < 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3 µg mL(-1) [95% CI 49.0-93.6]) than in non-fatal CM patients (48.0 µg mL(-1) [95% CI 37.7-58.2]; P = 0.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation-related marker that was independently associated with a fatal outcome (OR 1.084 for each ng mL(-1) increase [95% CI 1.017-1.156]; P = 0.014). Despite these laboratory derangements, no child in the study had clinically evident bleeding or thrombosis. An overt DIC score and high thrombomodulin levels are associated with a fatal outcome in CM, but infrequently indicate a consumptive coagulopathy.