Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

Optimizing Best Practice Advisory alerts in electronic medical records with a multi-pronged strategy at a tertiary care hospital in Singapore.

Objective: Clinical decision support (CDS) alerts can aid in improving patient care. One CDS functionality is the Best Practice Advisory (BPA) alert notification system, wherein BPA alerts are automated alerts embedded in the hospital's electronic medical records (EMR). However, excessive alerts can change clinician behavior; redundant and repetitive alerts can contribute to alert fatigue. Alerts can be optimized through a multipronged strategy. Our study aims to describe these strategies adopted and evaluate the resultant BPA alert optimization outcomes. Materials and Methods: This retrospective single-center study was done at Jurong Health Campus. Aggregated, anonymized data on patient demographics and alert statistics were collected from January 1, 2018 to December 31, 2021. "Preintervention" period was January 1-December 31, 2018, and "postintervention" period was January 1-December 31, 2021. The intervention period was the intervening period. Categorical variables were reported as frequencies and proportions and compared using the chi-square test. Continuous data were reported as median (interquartile range, IQR) and compared using the Wilcoxon rank-sum test. Statistical significance was defined at P < .05. Results: There was a significant reduction of 59.6% in the total number of interruptive BPA alerts, despite an increase in the number of unique BPAs from 54 to 360 from pre- to postintervention. There was a 74% reduction in the number of alerts from the 7 BPAs that were optimized from the pre- to postintervention period. There was a significant increase in percentage of overall interruptive BPA alerts with action taken (8 [IQR 7.7-8.4] to 54.7 [IQR 52.5-58.9], P-value < .05) and optimized BPAs with action taken (32.6 [IQR 32.3-32.9] to 72.6 [IQR 64.3-73.4], P-value < .05). We estimate that the reduction in alerts saved 3600 h of providers' time per year. Conclusions: A significant reduction in interruptive alert volume, and a significant increase in action taken rates despite manifold increase in the number of unique BPAs could be achieved through concentrated efforts focusing on governance, data review, and visualization using a system-embedded tool, combined with the CDS Five Rights framework, to optimize alerts. Improved alert compliance was likely multifactorial-due to decreased repeated alert firing for the same patient; better awareness due to stakeholders' involvement; and less fatigue since unnecessary alerts were removed. Future studies should prospectively focus on patients' clinical chart reviews to assess downstream effects of various actions taken, identify any possibility of harm, and collect end-user feedback regarding the utility of alerts.

Correction: Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

[This corrects the article DOI: 10.1371/journal.pone.0261234.].

Comparison of ROX index (SpO2/FIO2 ratio/respiratory rate) with a modified dynamic index incorporating PaO2/FIO2 ratio and heart rate to predict high flow nasal cannula outcomes among patients with acute respiratory failure: a single centre retrospective study.

BACKGROUND: High flow nasal cannula (HFNC) is increasingly being used to support patients with acute respiratory failure (ARF) and to avoid need for intubation. However, almost one third of the patients do not respond and require escalation of respiratory support. Previously, ROX index (SpO2/FIO2 [SF] ratio/respiratory rate) has been validated among pneumonia patients to facilitate early recognition of patients likely to fail HFNC and therefore, benefit from timely interventions. However, it has been postulated that incorporation of PaO2/FIO2 (PF) ratio from arterial blood gas (ABG) analysis may better predict the outcome of HFNC compared to indices that utilizes SF ratio. Similarly, heart rate increase after HFNC therapy initiation has been found to be associated with HFNC failure. Therefore, we aimed to compare ROX index with a new modified index to predict HFNC outcomes among ARF patients. MATERIALS AND METHODS: This single centre 2-year retrospective study included ARF patients of varying etiologies treated with HFNC. The modified index incorporated heart rate and substituted PF ratio for SF ratio in addition to respiratory rate. We named the index POX-HR and calculated Delta POX-HR index as the difference pre- and post-HFNC initiation POX-HR. We also recorded ROX index at the time when post-HFNC initiation ABG was done ('post-HFNC initiation ROX') and calculated Delta ROX. HFNC success was defined as no need of escalation of respiratory support or discharged to ward within 48 h of HFNC initiation, or successful wean off HFNC for at least 12 h. Evaluation was performed using area under the receiver operating characteristic curve (AUROC) and cut-offs assessed for prediction of HFNC outcomes. RESULTS: One hundred eleven patients were initiated on HFNC for ARF, of whom 72 patients (64.9%) had HFNC success. Patients with HFNC failure had significantly lower values for all the indices. At median of 3.33 h (IQR 1.48-7.24 h), Delta POX-HR demonstrated the best prediction accuracy (AUROC 0.813, 95% CI 0.726-0.900). A Delta POX-HR > 0.1 was significantly associated with a lower risk of HFNC failure. CONCLUSIONS: Our proposed modified dynamic index (Delta POX-HR) may facilitate early and accurate prediction of HFNC outcomes compared to ROX index among ARF patients of varied etiologies.

Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

BACKGROUND: Delaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction. METHODS: This was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation. RESULTS: HFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64-0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57-0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55-0.69)] and one hour later [AUC 0.63 (95% CI 0.56-0.70)]. CONCLUSION: The ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

Proton Pump Inhibitor Induced Subacute Cutaneous Lupus Erythematosus: A Case Series of 7 Patients and Brief Review of Literature.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) manifests with erythematous, nonscarring, annular, or papulosquamous plaques. Proton pump inhibitors (PPIs) are increasingly being incriminated in its causation, but reports of similar nature from India are lacking. AIMS: To describe the characteristics of seven patients with SCLE induced by PPIs and to review the published cases in order to provide a better perspective of the association. MATERIALS AND METHODS: We describe seven patients of PPI-induced SCLE, seen over a period of 6 years. We also review the literature for additional data on PPI-induced SCLE. The selected publications were reviewed, and relevant clinical and laboratory data were extracted. RESULTS: Of the total seven cases, there were four males and three females with a mean age of 60.2 ± 5.5 years (range 53-70 years). Nine episodes of PPI-induced SCLE were recorded in the seven patients. Of the initial episodes, esomeprazole was implicated in four, pantoprazole in two, and rabeprazole in one patient. Latency period ranged from 2 weeks to 1 year (mean 11.4 ± 16.2 weeks). Morphology was described as annular scaly plaques in six and papulosquamous in one. Antinuclear antibodies and anti-Ro antibodies were positive in all patients. Naranjo probability scale was used in all patients; two were categorized as definite and five as probable. Treatments included drug withdrawal in six patients, topical steroids in one, systemic corticosteroids in all seven, and hydroxychloroquine in one patient, used alone or in combinations. Complete remission was achieved in six cases, while one had partial remission. LIMITATION: Retrospective nature of this study and limited number of patients. CONCLUSION: PPIs can trigger SCLE.

High-flow nasal cannula therapy: A multicentred survey of the practices among physicians and respiratory therapists in Singapore.

BACKGROUND: Use of high-flow nasal cannula (HFNC) has become a regular intervention in the intensive care units especially in patients coming in with hypoxaemic respiratory failure. Clinical practices may differ from published literature. OBJECTIVES: The objective of this study was to determine the clinical practices of physicians and respiratory therapists (RTs) on the use of HFNC. METHODS: A retrospective observational study looking at medical records on HFNC usage from January 2015 to September 2017 was performed and was followed by a series of questions related to HFNC practices. The survey involved physicians and RTs in intensive care units from multiple centres in Singapore from January to April 2018. Indications and thresholds for HFNC usage with titration and weaning practices were compared with the retrospective observational study data. RESULTS: One hundred twenty-three recipients (69.9%) responded to the survey and reported postextubation (87.8%), pneumonia in nonimmunocompromised (65.9%), and pneumonia in immunocompromised (61.8%) patients as the top three indications for HFNC. Of all, 39.8% of respondents wanted to use HFNC for palliative intent. Similar practices were observed in the retrospective study with the large cohort of 63% patients (483 of the total 768 patients) where HFNC was used for acute hypoxaemic respiratory failure and 274 (35.7%) patients to facilitate extubation. The survey suggested that respondents would initiate HFNC at a lower fraction of inspired oxygen (FiO2), higher partial pressure of oxygen to FiO2 ratio, and higher oxygen saturation to FiO2 ratio for nonpneumonia patients than patients with pneumonia. RTs were less likely to start HFNC for patients suffering from pneumonia and interstitial lung disease than physicians. RTs also preferred adjustment of FiO2 to improve oxygen saturations and noninvasive ventilation for rescue. CONCLUSIONS: Among the different intensive care units surveyed, the indications and thresholds for the initiation of HFNC differed in the clinical practices of physicians and RTs.

Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS. METHODS: Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H2O) and low (<40mL/cm H2O) compliance were analysed. RESULTS: A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; P<0.01), and required a longer duration of ventilation (26 days, IQR 12-27 vs 8 days, IQR 5-15; P<0.01) and intensive care unit support (26 days, IQR 11-30 vs 11.5 days, IQR 7-17.3; P=0.01), with a higher incidence of acute kidney injury (15 patients [100%] vs 40 patients [46%]; P<0.01). There were 67 patients who had lung compliance data; 24 (35.8%) were classified as having high compliance and 43 (64.2%) as having low compliance. Mortality was higher in patients with high compliance (33.3% vs 11.6%; P=0.03), and was associated with a drop in compliance at day 7 (-9.3mL/cm H2O (IQR -4.5 to -15.4) vs 0.2mL/cm H2O (4.7 to -5.2) P=0.04). CONCLUSION: COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.

Predictors and outcomes of high-flow nasal cannula failure following extubation: A multicentre observational study.

INTRODUCTION: Despite adhering to criteria for extubation, up to 20% of intensive care patients require re-intubation, even with use of post-extubation high-flow nasal cannula (HFNC). This study aims to identify independent predictors and outcomes of extubation failure in patients who failed post-extubation HFNC. METHODS: We conducted a multicentre observational study involving 9 adult intensive care units (ICUs) across 5 public hospitals in Singapore. We included patients extubated to HFNC following spontaneous breathing trials. We compared patients who were successfully weaned off HFNC with those who failed HFNC (defined as re-intubation ≤7 days following extubation). Generalised additive logistic regression analysis was used to identify independent risk factors for failed HFNC. RESULTS: Among 244 patients (mean age: 63.92±15.51 years, 65.2% male, median APACHE II score 23.55±7.35), 41 (16.8%) failed HFNC; hypoxia, hypercapnia and excessive secretions were primary reasons. Stroke was an independent predictor of HFNC failure (odds ratio 2.48, 95% confidence interval 1.83-3.37). Failed HFNC, as compared to successful HFNC, was associated with increased median ICU length of stay (14 versus 7 days, P<0.001), ICU mortality (14.6% versus 2.0%, P<0.001) and hospital mortality (29.3% versus 12.3%, P=0.006). CONCLUSION: Post-extubation HFNC failure, especially in patients with stroke as a comorbidity, remains a clinical challenge and predicts poorer clinical outcomes. Our observational study highlights the need for future prospective trials to better identify patients at high risk of post-extubation HFNC failure.

In-hospital cardiac arrest incidence and outcomes in the era of COVID-19: an observational study in a Singapore hospital.

BACKGROUND: COVID-19 pandemic has resulted in significant strain on healthcare resources and this requires diligent resource re-allocation. We aim to describe the incidence and outcomes of in-hospital cardiac arrest (IHCA) during this period as compared to non-pandemic period. METHODS: We conducted a retrospective study in a tertiary care hospital in Singapore. The study compared the incidence and outcomes of code blue activations over a 3-month period from March to May 2020 (COVID-19 period) with the same months in 2019 (pre-COVID-19 period). The primary outcome of the study was the rate of survival to hospital discharge for IHCA. The secondary outcomes included incidence of all code blue activation per 1000 hospital admissions, incidence of IHCA per 1000 hospital admissions. OUTCOMES: The rate of survival to hospital discharge for IHCA was 5.88% in the COVID-19 period as compared to 10.0% in the pre-COVID-19 period [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.26-1.95]. Compared to pre-COVID-19 period, there were more IHCA incidences per 1000 hospital admissions in the COVID-19 period (1.86 vs 1.03; OR, 1.81; 95% CI, 0.78-4.41). CONCLUSIONS: The study observed a trend towards higher incidence of IHCA and lower rate of survival to hospital discharge during COVID-19 pandemic compared to pre-COVID-19 period.

Impact of implementing novel automated code blue activation system on in-hospital cardiac arrest: A single center study.

BACKGROUND: Prompt identification and management of patients having clinical deterioration on wards is one of the key steps to reduce in-hospital cardiac arrests (IHCA). Our organization implemented a novel Automated Code Blue Alert and Activation (ACBAA) system since 1st March 2018. METHODS: We conducted a retrospective before-and-after ACBAA system implementation study in JurongHealth Campus (JHC) of National University Health system (NUHS), Singapore. In JHC, code blue can be activated by both manual activation and ACBAA system activation from 1st March 2018. The ACBAA system will be activated when any of the pre-defined peri-arrest criteria is met. The primary outcome of the study was the incidence of IHCA. The secondary outcome included return of spontaneous circulation (ROSC) of IHCA and in-hospital survival to home discharge of code blue activation. OUTCOMES: The incidence of IHCA per 1000 hospital admissions after-ACBAA system implementation was 14.6% lower than before-ACBAA system though not statistically significant [relative risk (RR): 0.86, 95% confidence interval (CI) 0.55-1.34, P > 0.05]. Compared to the before-ACBAA system period, the after-ACBAA system period had a trend for higher rate of survival to home discharge after IHCA (RR: 2.13, 95% CI 0.65-6.93, P > 0.05) with good neurological outcome. CONCLUSIONS: Implementation of a novel ACBAA system has shown a trend in reducing IHCA incidence. In the era of digitalised healthcare system, the ACBAA system is practical and advisable to implement in order to reduce IHCA. Further studies are required to validate the criteria for peri-arrest code blue activation.

Stevens-Johnson Syndrome complicated by obstructive uropathy, pneumothorax, and pneumomediastinum: a case report and literature review.

BACKGROUND: Stevens-Johnson Syndrome (SJS) is an acute mucocutaneous eruption with blisters of the skin and haemorrhagic erosions of mucous membranes. This report describes air-leak syndrome and obstructive uropathy occurring simultaneously in a teenage patient affected by SJS. CASE PRESENTATION: A 17-year-old Malay female with SJS suffered from bilateral pneumothoraces, pneumomediastinum, and obstructive uropathy as early complications of her disease. She required intubation, chest tube insertion, and bilateral ureteric stenting as part of her intensive care management. These extra-cutaneous complications of renal and pulmonary systems were likely secondary to widespread epithelial detachment. CONCLUSION: Despite paucity of cases in adult literature, post-renal causes for acute kidney injury must be considered in SJS, especially in the setting of gross haematuria. Bedside point-of-care ultrasonography may be a useful tool for excluding obstructive uropathy. Pneumothorax is a rare but documented complication of SJS in paediatric cases and, to a lesser extent, adult patients. Extra care should be exercised when caring for mechanically ventilated patients suffering from SJS.

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

The effects of introduction of new observation charts and calling criteria on call characteristics and outcome of hospitalised patients.

OBJECTIVE: To determine the impact on call characteristics and patient outcomes since the implementation of a two-tiered rapid-response system along with new observation charts and calling criteria. DESIGN AND SETTING: A retrospective before-and-after study in an Australian tertiary referral hospital. PARTICIPANTS: Consecutive adult patients (_18 years), who had a rapid-response call between June and October 2009 ("before") and between June and October 2010 ("after"). MAIN OUTCOME MEASURES: Incidence of "serious adverse events" (cardiac arrests, unexpected deaths, and unplanned intensive care unit/high-dependency unit [HDU] admissions); subsequent illness severity and ICU/HDU and hospital mortality and length of stay; episodes of repeat calls for the same patient, time since admission and treatment limitation/ not-for-resuscitation order profiles. RESULTS: Statistically significant increase in number of rapid response calls from 14.3 to 21.2 per 1000 hospital admissions before and after, respectively (P < 0.001); this was associated with a 16% decrease in composite serious adverse events (not significant). There were no significant differences in the number of unplanned ICU/HDU admissions, admission severity scores and subsequent ICU/HDU and hospital mortality and length of stay. There was a significant increase in number of calls for patients who were admitted to hospital within 24 hours (2.5 v 4.7 per 1000 hospital admissions before and after, respectively; P < 0.05) and for patients who were transferred from acute care areas within 24 hours (3.7 v 6.2 per 1000 hospital admissions before and after, respectively; P < 0.05). There was a significant increase in number of repeat calls for the same patient (1.6 v 4.2 per 1000 hospital admissions before and after, respectively; P < 0.001); this was associated with higher mortality compared with single review in the after period (35.8% v 18.5%, respectively; P = 0.005). CONCLUSIONS: Implementation of a two-tiered rapid-response system and new observation charts and calling criteria increased the number of rapid-response calls with a nonsignificant trend towards a decreased incidence of serious adverse events. Further improvements in care of hospitalised patients may be possible by preventing repeat calls or calls within 24 hours of hospital admission and discharge from acute care areas.

Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an idiopathic, ulcerative, noninfective chronic inflammatory skin disorder of unknown etiology. It is associated with systemic medical illness in 50% of cases like inflammatory bowel disease, systemic arthritis, haematological diseases and malignancies. Characteristic lesions begin as pustule or vesiculopustule and progresses to an ulcer or deep erosion with violaceous overhanging or undermined borders. Diagnosis of pyoderma gangrenosum is clinical and depends on exclusion of other causes of cutaneous ulceration. The management of PG is treatment of underlying systemic medical illness and judicious use of immunosuppressants. Association of PG with these medical illnesses and treatment with immunosuppressants make the clinical utility for internists, gastroenterologists, haematologists and rheumatologists.

Raynaud's phenomenon.

Raynauds phenomena (RP) is a commonly encountered clinical manifestation which may be primary or secondary to underlying disease. There is imbalance between vasoconstricting and vasodilating factors. Physical examination, nailfold capillaroscopy and immunological tests can differentiate primary from secondary RP. Treatment involves prevention of RP so that permanent ischemic damage i.e. gangrene can be avoided. Avoidance of exposure to cold, emotional stress and certain drugs is mandatory and if attacks are occurring then vasodilators, prostaglandin analogues, anticoagulants and antiplatelet drugs may be added. An attempt has been made to guide the clinician to diagnose and treat a patient of RP through this article.

Pachydermoperiostosis with myelofibrosis and empty sella.

A case of pachydermoperiostosis presented to us in rheumatology clinic with complaints of pain and swelling in knee joints unresponsive to treatment, characteristic facial features, grade four clubbing of nails and broadening of distal parts of extremities. He also complained of fatiguability which was due to anemia. The natural history of the disease was reviewed and investigated.

Antiphospholipid antibody syndrome.

The 2006 International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome has increased the time between the two laboratory studies required for diagnosis from 6 to 12 weeks. Antibody to beta2 glycoprotein 1 has been included as a criterion. Various non-criteria diagnostic clues such as livedo reticularis, heart valve disease, thrombocytopenia, renal thrombotic microangiopathy, neurological manifestations, non-criteria antibodies (IgA aCL, IgA anti-beta2 glycoprotein I) and some research laboratory-identified antibodies (antiphosphatidylserine antibodies, antiphosphatidylethanolamine antibodies, antibodies against prothrombin alone and antibodies to the phosphatidylserine-prothrombin complex) have been recognised. New concepts of pathogenesis now implicate complement activation and participation of the innate immune system upstream to thrombosis. Warfarin remains the treatment of choice for patients who have suffered thrombosis, but antiplatelet agents and heparin are other options. Target INR is 2.0-3.0. The other drugs which are used in resistant cases are: rituximab, hydroxychloroquine, thrombin inhibitors and statins.