Summary Background India has the highest burden of acute coronary syndromes in the world, yet little is known about the treatments and outcomes of these diseases. We aimed to document the ...characteristics, treatments, and outcomes of patients with acute coronary syndromes who were admitted to hospitals in India. Methods We did a prospective registry study in 89 centres from 10 regions and 50 cities in India. Eligible patients had suspected acute myocardial infarction with definite electrocardiograph changes (whether elevated ST STEMI or non-STEMI or unstable angina), or had suspected myocardial infarction without ECG changes but with prior evidence of ischaemic heart disease. We recorded a range of clinical outcomes, and all-cause mortality at 30 days. Findings We enrolled 20 937 patients. Of the 20 468 patients who were given a definite diagnosis, 12 405 (60·6%) had STEMI. The mean age of these patients was 57·5 (SD 12·1) years; patients with STEMI were younger (56·3 12·1 years) than were those with non-STEMI or unstable angina (59·3 11·8 years). Most patients were from lower middle 10 737 (52·5%) and poor 3999 (19·6%) social classes. The median time from symptoms to hospital was 360 (IQR 123–1317) min, with 50 (25–68) min from hospital to thrombolysis. 6226 (30·4%) patients had diabetes; 7720 (37·7%) had hypertension; and 8242 (40·2%) were smokers. Treatments for STEMI differed from those for non-STEMI or unstable angina. More patients with STEMI than with non-STEMI were given anti-platelet drugs (98·2% vs 97·4%); angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) (60·5% vs 51·2%); and percutaneous coronary interventions (8·0% vs 6·7%, p<0·0001 for all comparisons). Thrombolytics (96·3% streptokinase) were used for 58·5% of patients with STEMI. Conversely, fewer patients with STEMI than those with non-STEMI or unstable angina were given β blockers (57·5% vs 61·9%); lipid-lowering drugs (50·8% vs 53·9%); and coronary bypass graft surgery (1·9% vs 4·4%, p<0·0001 for all comparisons). The 30-day outcomes for patients with STEMI were death (8·6%), reinfarction (2·3%), and stroke (0·7%). Outcomes for those with non-STEMI or unstable angina were better: death (3·7%), reinfarction (1·2%), and stroke (0·3%, p<0·0001 for all comparisons). Use of key treatments also differed by socioeconomic status: more rich patients than poor patients were given thrombolytics (60·6% vs 52·3%), β blockers (58·8% vs 49·6%), lipid-lowering drugs (61·2% vs 36·0%), ACE inhibitors or ARB (63·2% vs 54·1%), percutaneous coronary intervention (15·3% vs 2·0%), and coronary artery bypass graft surgery (7·5% vs 0·7%, p<0·0001 for all comparisons). Mortality was higher for poor patients than for rich patients (8·2% vs 5·5%, p<0·0001). Adjustment for treatments (but not risk factors and baseline characteristics) eliminated this difference in mortality. Interpretation Patients in India who have acute coronary syndromes have a higher rate of STEMI than do patients in developed countries. Since most of these patients were poor, less likely to get evidence-based treatments, and had greater 30-day mortality, reduction of delays in access to hospital and provision of affordable treatments could reduce morbidity and mortality. Funding Division of Clinical Trials, St John's Research Institute, Bangalore, India; Population Health Research Institute (PHRI), McMaster University, Canada; Sanofi-Aventis India.
Surgical site infections (SSIs) occur frequently and impact patients and health care systems. Remote surveillance of surgical wounds is currently limited by the need for manual assessment by ...clinicians. Machine learning (ML)-based methods have recently been used to address various aspects of the postoperative wound healing process and may be used to improve the scalability and cost-effectiveness of remote surgical wound assessment.
The objective of this review was to provide an overview of the ML methods that have been used to identify surgical wound infections from images.
We conducted a scoping review of ML approaches for visual detection of SSIs following the JBI (Joanna Briggs Institute) methodology. Reports of participants in any postoperative context focusing on identification of surgical wound infections were included. Studies that did not address SSI identification, surgical wounds, or did not use image or video data were excluded. We searched MEDLINE, Embase, CINAHL, CENTRAL, Web of Science Core Collection, IEEE Xplore, Compendex, and arXiv for relevant studies in November 2022. The records retrieved were double screened for eligibility. A data extraction tool was used to chart the relevant data, which was described narratively and presented using tables. Employment of TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines was evaluated and PROBAST (Prediction Model Risk of Bias Assessment Tool) was used to assess risk of bias (RoB).
In total, 10 of the 715 unique records screened met the eligibility criteria. In these studies, the clinical contexts and surgical procedures were diverse. All papers developed diagnostic models, though none performed external validation. Both traditional ML and deep learning methods were used to identify SSIs from mostly color images, and the volume of images used ranged from under 50 to thousands. Further, 10 TRIPOD items were reported in at least 4 studies, though 15 items were reported in fewer than 4 studies. PROBAST assessment led to 9 studies being identified as having an overall high RoB, with 1 study having overall unclear RoB.
Research on the image-based identification of surgical wound infections using ML remains novel, and there is a need for standardized reporting. Limitations related to variability in image capture, model building, and data sources should be addressed in the future.
We conducted a feasibility 2×2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in ...patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph's Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥90% of eligible patients; and 3) >90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes.
Using computerized randomization, patients were allocated to one of four groups: NMDA active with steroid placebo; NMDA placebo with steroid active; both NMDA and steroid active; both NMDA and steroid placebo. Patients, health providers, and data analysts were blinded to allocation. Patients were followed for 3 months after randomization.
The trial was initiated in May 2017 at Hamilton and, after subsequent regulatory and ethics approval, in April 2018 at Cleveland. The trial had to be stopped after only 1 month of recruitment in Cleveland because the packaged study medications (memantine) expired and we were unable to procure the dosage required. Among 41 eligible patients, 27 (66%) were randomized. The recruitment rate/week was 0.63, 95% confidence interval (CI): 0.47-0.79 in Hamilton; and 1, 95% CI: 0.83-1.17 in Cleveland. Follow-up was complete for all 24 patients (100%) in Hamilton, and 3 of 4 patients in Cleveland. In total, only 4 patients (15%), and 2 patients (7%) had persistent pain at rest and with movement, respectively. There were no significant differences between groups for other outcomes.
The trial had to be stopped prematurely due to non-availability of study medications. Trial feasibility objectives of recruiting 90% of eligible patients and recruiting at least one patient/week per site were not met. Consideration for protocol changes will be necessary for the full trial.
NCT02950233.
There is a need to identify and test low-cost approaches for cardiovascular disease (CVD) risk reduction that can enable health systems to achieve such a strategy.
Community health workers (CHWs) are ...an integral part of health-care delivery system in lower income countries. Our aim was to assess impact of CHW based interventions in reducing CVD risk factors in rural households in India.
We performed an open-label cluster-randomized trial in 28 villages in 3 states of India with the household as a unit of randomization. Households with individuals at intermediate to high CVD risk were randomized to intervention and control groups. In the intervention group, trained CHWs delivered risk-reduction advice and monitored risk factors during 6 household visits over 12 months. Households in the non-intervention group received usual care. Primary outcomes were a reduction in systolic BP (SBP) and adherence to prescribed BP lowering drugs.
We randomized 2312 households (3261 participants at intermediate or high risk) to intervention (1172 households) and control (1140 households). At baseline prevalence of tobacco use (48.5%) and hypertension (34.7%) were high. At 12 months, there was significant decline in SBP (mmHg) from baseline in both groups- controls 130.3 ± 21 to 128.3 ± 15; intervention 130.3 ± 21 to 127.6 ± 15 (P < .01 for before and after comparison) but there was no difference between the 2 groups at 12 months (P = .18). Adherence to antihypertensive drugs was greater in intervention vs control households (74.9% vs 61.4%, P = .001).
A 12-month CHW-led intervention at household level improved adherence to prescribed drugs, but did not impact SBP. To be more impactful, a more comprehensive solution that addresses escalation and access to useful therapies is needed.
Abstract Objectives A P -value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost ...with small changes in the numbers of outcomes. Study Design and Setting A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P -value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result. Results The 399 eligible trials had a median sample size of 682 patients (range: 15–112,604) and a median of 112 events (range: 8–5,142); 53% reported a P -value <0.01. The median Fragility Index was 8 (range: 0–109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up. Conclusion The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P -value and helps identify less robust results.
Investigators designing clinical trials often use composite outcomes to overcome many statistical issues. Trialists want to maximize power to show a statistically significant treatment effect and ...avoid inflation of Type I error rate due to evaluation of multiple individual clinical outcomes. However, if the treatment effect is not similar among the components of this composite outcome, we are left not knowing how to interpret the treatment effect on the composite itself. Given significant heterogeneity among these components, a composite outcome may be judged as being invalid or un-interpretable for estimation of the treatment effect. This paper compares the power of different tests to detect heterogeneity of treatment effect across components of a composite binary outcome.
Simulations were done comparing four different models commonly used to analyze correlated binary data. These models included: logistic regression for ignoring correlation, logistic regression weighted by the intra cluster correlation coefficient, population average logistic regression using generalized estimating equations (GEE), and random effects logistic regression.
We found that the population average model based on generalized estimating equations (GEE) had the greatest power across most scenarios. Adequate power to detect possible composite heterogeneity or variation between treatment effects of individual components of a composite outcome was seen when the power for detecting the main study treatment effect for the composite outcome was also reasonably high.
It is recommended that authors report tests of composite heterogeneity for composite outcomes and that this accompany the publication of the statistically significant results of the main effect on the composite along with individual components of composite outcomes.
Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery.
To examine the characteristics and short-term outcome of perioperative MI.
Cohort ...study. (ClinicalTrials.gov registration number: NCT00182039)
190 centers in 23 countries.
8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial.
Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI.
Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 95% CI, 2.68 to 8.43) and without (12.5%; adjusted odds ratio, 4.00 CI, 2.65 to 6.06) ischemic symptoms.
Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed.
Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.
Timely identification of patients at a high risk of clinical deterioration is key to prioritizing care, allocating resources effectively, and preventing adverse outcomes. Vital signs-based, ...aggregate-weighted early warning systems are commonly used to predict the risk of outcomes related to cardiorespiratory instability and sepsis, which are strong predictors of poor outcomes and mortality. Machine learning models, which can incorporate trends and capture relationships among parameters that aggregate-weighted models cannot, have recently been showing promising results.
This study aimed to identify, summarize, and evaluate the available research, current state of utility, and challenges with machine learning-based early warning systems using vital signs to predict the risk of physiological deterioration in acutely ill patients, across acute and ambulatory care settings.
PubMed, CINAHL, Cochrane Library, Web of Science, Embase, and Google Scholar were searched for peer-reviewed, original studies with keywords related to "vital signs," "clinical deterioration," and "machine learning." Included studies used patient vital signs along with demographics and described a machine learning model for predicting an outcome in acute and ambulatory care settings. Data were extracted following PRISMA, TRIPOD, and Cochrane Collaboration guidelines.
We identified 24 peer-reviewed studies from 417 articles for inclusion; 23 studies were retrospective, while 1 was prospective in nature. Care settings included general wards, intensive care units, emergency departments, step-down units, medical assessment units, postanesthetic wards, and home care. Machine learning models including logistic regression, tree-based methods, kernel-based methods, and neural networks were most commonly used to predict the risk of deterioration. The area under the curve for models ranged from 0.57 to 0.97.
In studies that compared performance, reported results suggest that machine learning-based early warning systems can achieve greater accuracy than aggregate-weighted early warning systems but several areas for further research were identified. While these models have the potential to provide clinical decision support, there is a need for standardized outcome measures to allow for rigorous evaluation of performance across models. Further research needs to address the interpretability of model outputs by clinicians, clinical efficacy of these systems through prospective study design, and their potential impact in different clinical settings.
IntroductionIn non-elderly adults, aortic valve replacement (AVR) with conventional prostheses yield poor long-term outcomes. Recent publications suggest a benefit of the Ross procedure over ...conventional AVR and highlight the need for high-quality randomised controlled trial (RCTs) on the optimal AVR. We have initiated a pilot trial assess two feasibility criteria and one assumption: (1) evaluate the capacity to enrol six patients per centre per year in at least five international centre, (2) validate greater than 90% compliance with allocation and (3) to validate the proportion of mechanical (≥65%) vs biological (≤35%) valves in the conventional arm.Methods and analysisRoss for Valve replacement In AduLts (REVIVAL) is a multinational, expertise-based RCT in adults aged 18–60 years undergoing AVR, comparing the Ross procedure versus one of the alternative approaches (mechanical vs stented or stentless bioprosthesis). The feasibility objectives will be assessed after randomising 60 patients; we will then make a decision regarding whether to expand the trial with the current protocol. We will ultimately examine the impact of the Ross procedure as compared with conventional AVR in non-elderly adults on survival free of valve-related life-threatening complications (major bleeding, systemic thromboembolism, valve thrombosis and valve reoperation) over the duration of follow-up. The objectives of the pilot trial will be analysed using descriptive statistics. In the full trial, the intention-to-treat principle will guide all primary analyses. A time-to-event analysis will be performed and Kaplan-Meier survival curves with comparison between groups using a log rank test will be presented.Ethics and disseminationREVIVAL will answer whether non-elderly adults benefit from the Ross procedure over conventional valve replacement. The final results at major meetings, journals, regional seminars, hospital rounds and via the Reducing Global Perioperative Risk Multimedia Resource Centre.Trial registration numberClinicalTrials.gov Identifier: NCT03798782Protocol versionJanuary 29, 2019 (Final Version 1.0)
Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin ...(GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients.
Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence.
Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI -0.5 to 0.07 I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI 0.20 to 0.64 I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI 1.17 to 3.37, I2 = 49); fatigue (RR = 1.85, 95% CI 1.12 to 3.05, I2 = 0); difficulties with mentation (RR = 3.34, 95% CI 1.54 to 7.25, I2 = 0); and visual disturbances (RR = 5.72, 95% CI 1.94 to 16.91, I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements.
Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue.
PROSPERO CRD42016034040.
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