Improving results management processes in an acute hospital using a multi-faceted approach.

BACKGROUND: Radiological examinations and laboratory tests are routinely ordered by hospital physicians as part of the care plan to diagnose and treat patients. However, the failure to actively review and follow-up on these results pose a significant problem to patient safety. A study team was formed to mitigate the clinical risks of poor results management, which was identified as a top clinical risk in our organization, in order to make improvements to the results management process and to ensure the timely review, acknowledgement and follow-up of test results. OBJECTIVE: This study was carried out to improve results management processes and ensure the timely review, acknowledgment, and follow-up of test results, in order to mitigate the clinical risks posed to patient safety. METHODS: The institutional expectations of results management were set and published as a hospital policy, which was communicated to all clinical departments for compliance. Improvements to the electronic medical records system were made to facilitate the results acknowledgement process, and physicians were engaged to educate them on the importance of results management. RESULTS: The study team observed a decrease in unacknowledged results from approximately 16 000 in March 2017 to 2673 in December 2020. The compliance rate for acknowledgement results increased from a monthly average of 83.7% (from March to December 2017) to a monthly average of 99.3% (in 2020). The risk score for results management decreased from 16 to 6.5 and was excluded from the organization's top clinical risks. CONCLUSION: This study showed the importance of both system improvements and culture changes that are required to improve the process of results management and provides a step forward for the hospital to safeguard patient safety and mitigate clinical risk.

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

PURPOSE: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. METHODS: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). RESULTS: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). CONCLUSION: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Assessing the Impact of a Pulmonary Embolism Response Team and Treatment Protocol on Patients Presenting With Acute Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) care has traditionally been fragmented. The newly introduced Pulmonary Embolism Response Team (PERT) model provides streamlined care based on expedient, multi-disciplinary decision-making. This study aimed to quantify the impact of PERT, as part of a hospital-wide PE treatment protocol, on clinical outcomes. METHODS: Consecutive adult patients with acute PE diagnosed via computed tomography pulmonary angiogram (CTPA) were included. The PERT and treatment protocol were introduced in January 2015. Patient characteristics, therapies, quality measures of CTPA reporting, and clinical outcomes of PE patients treated for 2 years before and after implementation of these changes were evaluated. Primary endpoints were median length of stay in intensive care (ICU) and survival to discharge. RESULTS: A total of 321 consecutive PE patients were enrolled, of which 154 (treated in 2013-2014) and 167 (2015-2016) patients formed the historical control and study groups, respectively. Implementation of the algorithm was associated with less variance in anticoagulation and improved reporting of right heart strain parameters on CTPA. The ICU stay was reduced from a median of 5 to 2 days (p < 0.01). Eligible massive PE patients receiving reperfusion increased from 30% to 92% (p = 0.01), with mean delay from diagnosis to reperfusion decreasing from 763 to 181 minutes (p < 0.01). Bleeding complications were not increased, but overall survival to discharge remained unchanged. CONCLUSIONS: Introducing a PERT and treatment protocol reduced ICU stay, enhanced quality measures, and improved access of massive PE patients to reperfusion therapies, without increasing bleeding complications or health care costs.

Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial.

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy. RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P < 0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3 months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P = 0.001), but not frequency of INR measurements, was lower at 1, 2, and 3 months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R2 = 42.4% (P < 0.001) and mean percentage error of -7.4%. CONCLUSIONS: Among Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.

Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

OBJECTIVES: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. BACKGROUND: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. METHODS: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year. RESULTS: A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year. CONCLUSIONS: In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year.

Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: The double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarction (AMI). METHODS: Patients presenting with AMI to a percutaneous coronary intervention-capable hospital in Singapore between January 2014 and March 2021 were retrospectively studied. Patients were stratified into the following: (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. Obesity and malnutrition were defined according to the World Health Organization definition (body mass index ≥27.5 kg/m2) and Controlling Nutritional Status score, respectively. The primary outcome was all-cause mortality. The association between combined obesity and nutritional status with mortality was examined using Cox regression, adjusted for age, sex, AMI type, previous AMI, ejection fraction, and chronic kidney disease. Kaplan-Meier curves for all-cause mortality were constructed. RESULTS: The study included 1829 AMI patients, of which 75.7% were male and mean age was 66 years. Over 75% of patients were malnourished. Majority were malnourished nonobese (57.7%), followed by malnourished obese (18.8%), nourished nonobese (16.9%), and nourished obese (6.6%). Malnourished nonobese had highest all-cause mortality (38.6%), followed by the malnourished obese (35.8%), nourished nonobese (21.4%), and nourished obese (9.9%, P<0.001). Kaplan-Meier curves demonstrated least favorable survival in malnourished nonobese group, followed by malnourished obese, nourished nonobese, and nourished obese. With nourished nonobese group as the reference, malnourished nonobese had higher all-cause mortality (hazard ratio, 1.46 [95% CI, 1.10-1.96], P=0.010), but only a nonsignificant increase in mortality was observed in the malnourished obese (hazard ratio, 1.31 [95% CI, 0.94-1.83], P=0.112). CONCLUSIONS: Among AMI patients, malnutrition is prevalent even in the obese. Compared to nourished patients, malnourished AMI patients have a more unfavorable prognosis especially in those with severe malnutrition regardless of obesity status, but long-term survival is the most favorable among nourished obese patients.

Characteristics and outcomes of young patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: retrospective analysis in a multiethnic Asian population.

OBJECTIVE: ST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention. METHODS: Data from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (<50 years old) or older (≥50 years old) groups. RESULTS: Of the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were <50 years old. Young compared with older patients were more likely to be male, current smokers, of Indian ethnicity, have family history of ischaemic heart disease (IHD) and had lower 1 year mortality (3.4% vs 10.4%, p<0.0001). Although diabetes, hypertension or dyslipidaemia was less common among young patients, the prevalence of having any one of these risk factors was high in the range of 28% to 38%. Age was an independent predictor of mortality in the older but not younger patients with STEMI, and diabetes showed a trend towards mortality in both groups. CONCLUSION: Young patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.

Sleep apnea and diabetes mellitus are independently associated with cardiovascular events and hospitalization for heart failure after coronary artery bypass grafting.

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (-), sleep apnea (-) DM (+), and sleep apnea (-) DM (-) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (-), 13% in the sleep apnea (-) DM (+), and 5% in the sleep apnea (-) DM (-) groups. Using sleep apnea (-) DM (-) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7-6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0-52.3; p < 0.001). Sleep apnea and DM have independent effects on the prognosis of patients undergoing CABG.Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.

Screening and treatment of obstructive sleep apnea in acute coronary syndrome. A randomized clinical trial.

BACKGROUND: We evaluated the effects of sleep-study guided multidisciplinary therapy (SGMT) of obstructive sleep apnoea (OSA) in patients presenting with acute coronary syndrome. METHODS: Eligible patients were randomized into (1) SGMT, comprised a sleep study during the index admission and continuous positive airway pressure and behavioral therapy for those with at least mild OSA or (2) standard therapy. The primary end point was the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level from baseline to the 7-month follow-up. RESULTS: A total of 159 patients completed the trial. Of the 70 patients randomized to SGMT, 21 (30%), 15 (22%) and 27 (39%) were diagnosed with mild, moderate and severe OSA, respectively. Continuous positive airway pressure and a positional pillow were prescribed to 57 (91%) and 6 (9%) patients with OSA. Although plasma NT-proBNP levels were lower after 7 months compared to the baseline, the levels did not differ significantly between the SGMT and standard therapy groups at baseline (579 ±â€¯1117 vs. 611 ±â€¯899 pg/dL, p = .851) or at 7 months (90 ±â€¯167 vs. 93 ±â€¯174 pg/dL, p = .996). The changes in NT-proBNP levels from baseline to 7 months were similar with SGMT and standard therapy (-489 vs. -518 pg/dL, p = .726). Similar findings were observed for the plasma ST2 and hs-CRP levels. CONCLUSIONS: OSA screening and multifaceted treatment during the sub-acute phase of acute coronary syndrome did not further reduce the levels of cardiovascular biomarkers when compared with standard therapy. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov NCT02599298.

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

OBJECTIVE: Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG. METHODS: This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG. RESULTS: Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness. CONCLUSION: Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT02701504.

An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: A phase I, double blind, randomized, placebo-controlled, study of two dosages.

BACKGROUND: Hand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide. METHODS: In this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks. RESULTS: Of 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated. CONCLUSION: These data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children.

Sleep study-guided multidisciplinary therapy (SGMT) for patients with acute coronary syndrome: Trial rationale and design.

Obstructive sleep apnea (OSA) is an emerging risk marker for acute coronary syndrome (ACS). This randomized trial aims to determine the effects of sleep study-guided multidisciplinary therapy (SGMT) comprising overnight sleep study, continuous positive airway pressure, and behavioral therapy for OSA during the subacute phase of ACS. We hypothesize that SGMT will reduce (1) the plasma levels of N-terminal pro brain natriuretic peptide and suppression of tumorigenicity 2; (2) the estimated 10-year risk of cardiovascular mortality as measured by the European Systematic Coronary Risk Evaluation (SCORE) algorithm; and (3) the cardiovascular event rate during a 3-year follow-up, compared with standard therapy. In the SGMT trial, 180 patients presenting with ACS will be randomly assigned to SGMT (n = 90) and standard therapy (n = 90) groups. Both groups will receive guideline-mandated treatment for ACS. Those assigned to SGMT will additionally undergo a sleep study and, if OSA is diagnosed, attend a multidisciplinary OSA clinic where they will receive personalized treatment including continuous positive airway pressure and behavioral/lifestyle counseling. The primary endpoint is the plasma N-terminal pro brain natriuretic peptide concentration at 7-month follow-up. This report presents the baseline characteristics of 117 patients (SGMT group: n =54; standard therapy group: n =63) who had been enrolled into the study as of August 31, 2017. The results of this trial will help us to understand whether active OSA diagnosis and treatment will improve the physiologic and clinical cardiovascular outcomes of this group of patients.

Spontaneous adrenal haemorrhage after catheter ablation of supraventricular tachycardia.

Catheter ablation is established as a first-line therapy for most patients with recurrent supraventricular tachycardia (SVT), with high success rates and very low complication rates. A 60-year-old woman developed severe right flank pain following straightforward catheter ablation for SVT. This was caused by a spontaneous right adrenal haemorrhage, which, after much delay, was eventually recognised as the cause of her symptoms. Adrenal haematomas are rare and, to the best of our knowledge, this is the first reported case of spontaneous adrenal haemorrhage occurring after any interventional cardiac procedure. Clinicians should be aware of this rare but potentially serious complication and consider it as a differential diagnosis in any patient with severe flank pain following interventional cardiac procedures, to prevent delays in diagnosis.

Safety, potential efficacy, and pharmacokinetics of specific polyclonal immunoglobulin F(ab')2 fragments against avian influenza A (H5N1) in healthy volunteers: a single-centre, randomised, double-blind, placebo-controlled, phase 1 study.

BACKGROUND: Human infection with the avian influenza A H5N1 virus results in disease with a high fatality rate, against which antiviral treatments have limited efficacy. We aimed to investigate the safety, pharmacokinetics, and therapeutic potential of specific polyclonal immunoglobulin equine F(ab')2 fragments raised against influenza A/Vietnam/1194/2004 virus (H5N1 subtype) in healthy volunteers. METHODS: We did a randomised, double-blind, placebo-controlled, single-centre phase 1 study. In stage 1 (one infusion) and stage 2 (five infusions) of the trial, we randomly assigned healthy male volunteers to receive once-daily intravenous infusions of 0·85 U/kg body weight of F(ab')2 or once-daily saline placebo. Randomisation was done centrally, with one block of four patients and one block for substitutes (three actives, one placebo) in stage 1, and two blocks of six patients (five actives and one placebo) and the same block for substitutes in stage 2. The primary objective was assessment of the clinical and laboratory safety of F(ab')2, which was monitored for 22 days in the group that received one dose (assessments on days 0-2, 4, 8, 15, and 22) and 33 days in the group that received five doses (days 0-6, 8, 10, 12, 19, 26, and 33). A final post-study safety assessment was done at 120 days. We also assessed pharmacokinetic outcomes, and assayed haemagglutination and seroneutralisation activity. Analysis was done according to intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02295813. FINDINGS: We enrolled 16 healthy Asian men between Sept 28 and Dec 28, 2012, and randomly assigned 13 to one or five doses of F(ab')2 and three to placebo. F(ab')2 was well tolerated, and no deaths or serious adverse events occurred. Three patients had mild adverse events (one each of blepharospasm, sinusitis, and pyrexia). The pyrexia (38°C) was regarded as probably related to the infusion, and resolved after 37 min. Our laboratory assessments of blood and urine samples and physical examinations of heart rate, electrocardiogram readings, and weight showed no clinically significant safety issues. Mean peak plasma concentrations were 19·3 µg/mL (SD 3·5) with the one dose schedule and 23·0 µg/mL (4·5) with the five-dose schedule. F(ab')2 were still detectable in plasma on average up to 5 days after five doses. Haemagglutination inhibition was only increased after the third dose, but in-vitro seroneutralisation activity was transiently increased after each of the five doses to concentrations regarded as clinically beneficial in infected patients. INTERPRETATION: F(ab')2 showed good safety, tolerability, and therapeutic potential for managing of H5N1 exposed patients. FUNDING: Fab'entech.

Pulmonary embolism as a cause of unexplained sinus tachycardia after right ventricular myocardial infarction.

We present the case of a patient who developed new-onset asymptomatic sinus tachycardia after undergoing treatment for a right ventricular myocardial infarction. Even after excluding heart failure, infection and bleeding, the sinus tachycardia persisted. Computed tomography pulmonary angiography showed multiple bilateral pulmonary emboli. The vital sign abnormality resolved after treatment with an anticoagulant. We postulate that the pulmonary emboli originated from thrombi that were formed in the infarcted and dysfunctional right ventricle. Pulmonary embolism is a very rare complication of right ventricular myocardial infarction, and patients usually present with pleuritic chest pain. Our case highlights that asymptomatic sinus tachycardia could be a presenting feature of pulmonary embolism after the occurrence of a right ventricular myocardial infarction. A high index of suspicion is warranted in order to detect this potentially lethal complication.