Wearable sensors for prediction of intraamniotic infection in women with preterm premature rupture of membranes: a prospective proof of principle study.

PURPOSE: To evaluate the use of wearable sensors for prediction of intraamniotic infection in pregnant women with PPROM. MATERIALS AND METHODS: In a prospective proof of principle study, we included 50 patients diagnosed with PPROM at the University Hospital Zurich between November 2017 and May 2020. Patients were instructed to wear a bracelet during the night, which measures physiological parameters including wrist skin temperature, heart rate, heart rate variability, and breathing rate. A two-way repeated measures ANOVA was performed to evaluate the difference over time of both the wearable device measured parameters and standard clinical monitoring values, such as body temperature, pulse, leucocytes, and C-reactive protein, between women with and without intraamniotic infection. RESULTS: Altogether, 23 patients (46%) were diagnosed with intraamniotic infection. Regarding the physiological parameters measured with the bracelet, we observed a significant difference in breathing rate (19 vs 16 per min, P < .01) and heart rate (72 vs 67 beats per min, P = .03) in women with intraamniotic infection compared to those without during the 3 days prior to birth. In parallel to these changes standard clinical monitoring values were significantly different in the intraamniotic infection group compared to women without infection in the 3 days preceding birth. CONCLUSION: Our results suggest that wearable sensors are a promising, noninvasive, patient friendly approach to support the early detection of intraamniotic infection in women with PPROM. However, confirmation of our findings in larger studies is required before implementing this technique in standard clinical management.

Can Wrist-Worn Medical Devices Correctly Identify Ovulation?

(1) Background: Hormonal fluctuations across the menstrual cycle lead to multiple changes in physiological parameters such as body temperature, cardiovascular function, respiratory rate and perfusion. Electronic wearables analyzing those parameters might present a convenient alternative to urinary ovulation tests for predicting the fertile window. (2) Methods: We conducted a prospective observational study including women aged 18-45 years without current hormonal therapy who used a wrist-worn medical device and urinary ovulation tests for a minimum of three cycles. We analyzed the accuracy of both the retrospective and prospective algorithms using a generalized linear mixed-effects model. The findings were compared to real-world data from bracelet users who also reported urinary ovulation tests. (3) Results: A total of 61 study participants contributing 205 cycles and 6081 real-life cycles from 3268 bracelet users were included in the analysis. The mean error in identifying ovulation with the wrist-worn medical device retrospective algorithm in the clinical study was 0.31 days (95% CI -0.13 to 0.75). The retrospective algorithm identified 75.4% of fertile days, and the prospective algorithm identified 73.8% of fertile days correctly within the pre-specified equivalence limits (±2 days). The quality of the retrospective algorithm in the clinical study could be confirmed by real-world data. (4) Conclusion: Our data indicate that wearable sensors may be used to accurately detect the periovulatory period.

Changes in Heart Rate, Heart Rate Variability, Breathing Rate, and Skin Temperature throughout Pregnancy and the Impact of Emotions-A Longitudinal Evaluation Using a Sensor Bracelet.

(1) Background: Basic vital signs change during normal pregnancy as they reflect the adaptation of maternal physiology. Electronic wearables like fitness bracelets have the potential to provide vital signs continuously in the home environment of pregnant women. (2) Methods: We performed a prospective observational study from November 2019 to November 2020 including healthy pregnant women, who recorded their wrist skin temperature, heart rate, heart rate variability, and breathing rate using an electronic wearable. In addition, eight emotions were assessed weekly using five-point Likert scales. Descriptive statistics and a multivariate model were applied to correlate the physiological parameters with maternal emotions. (3) Results: We analyzed data from 23 women using the electronic wearable during pregnancy. We calculated standard curves for each physiological parameter, which partially differed from the literature. We showed a significant association of several emotions like feeling stressed, tired, or happy with the course of physiological parameters. (4) Conclusions: Our data indicate that electronic wearables are helpful for closely observing vital signs in pregnancy and to establish modern curves for the physiological course of these parameters. In addition to physiological adaptation mechanisms and pregnancy disorders, emotions have the potential to influence the course of physiological parameters in pregnancy.

Prevalence of latent structural heart disease in Nepali schoolchildren.

BACKGROUND: The present study aimed to quantify the burden of structural heart disease in Nepali children. METHODS: We performed a school-based cross-sectional echocardiographic screening study with cluster random sampling among children 5-16 years of age. RESULTS: Between December 2012 and January 2019, 6573 children (mean age 10.6 ± 2.9 years) from 41 randomly selected schools underwent echocardiographic screening. Structural heart disease was detected in 14.0 per 1000 children (95% CI 11.3-17.1) and was congenital in 3.3 per 1000 (95% CI 2.1-5.1) and rheumatic in 10.6 per 1000 (95% CI 8.3-13.4). Rates of rheumatic heart disease were higher among children attending public as compared to private schools (OR 2.8, 95% CI 1.6-5.2, p = 0.0001). CONCLUSION: Rheumatic heart disease accounted for three out of four cases of structural heart disease and was more common among children attending public as compared to private schools.

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve.

BACKGROUND: We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS: Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS: A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS: In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Biodegradable polymer sirolimus-eluting stents vs durable polymer everolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis of individual patient data from 5 randomized trials.

BACKGROUND: Newest generation drug-eluting stents combine biodegradable polymers with ultrathin stent platforms in order to minimize vessel injury and inflammatory response. Evidence from randomized controlled trials suggested that differences in stent design translate into differences in clinical outcome. The aim of the present study was to evaluate the safety and efficacy of ultrathin strut, biodegradable polymer sirolimus eluting stents (BP SES) compared with thin strut, durable polymer everolimus-eluting stents (DP EES) among patients undergoing percutaneous coronary intervention (PCI). METHODS: We pooled individual participant data from 5 randomized trials (NCT01356888, NCT01939249, NCT02389946, NCT01443104, NCT02579031) including a total of 5,780 patients, and performed a one-stage meta-analysis using a mixed effects Cox regression model. RESULTS: At a median duration of follow-up of 739 days (interquartile range 365-1,806 days), target-lesion failure occurred in 337 (10.3%) and 304 (12.2%) patients treated with BP SES and DP EES (HR 0.86, 95%CI 0.71-1.06, P = .16). There were no significant differences between BP SES and DP EES with regards to cardiac death (111 (3.4%) vs 102 (4.1%); HR 1.05, 95%CI 0.80-1.37, P = .73), target-vessel myocardial infarction (136 (4.1%) vs 126 (5.0%), HR 0.79, 95%CI 0.62-1.01, P = .061), and clinically-driven target-lesion revascularization (163 (5.0%) vs 147 (5.9%); HR 0.94, 95%CI 0.75-1.18, P = .61). The effect was consistent across major subgroups. In a landmark analysis, there was no significant interaction between treatment effect and timing of events. CONCLUSIONS: In this patient-level meta-analysis of 5 randomized controlled trials, BP SES were associated with a similar risk of target-lesion failure compared with DP EES among patients undergoing PCI. STUDY REGISTRATION: PROSPERO registry (CRD42018109098).

The Accuracy of Wrist Skin Temperature in Detecting Ovulation Compared to Basal Body Temperature: Prospective Comparative Diagnostic Accuracy Study.

BACKGROUND: As a daily point measurement, basal body temperature (BBT) might not be able to capture the temperature shift in the menstrual cycle because a single temperature measurement is present on the sliding scale of the circadian rhythm. Wrist skin temperature measured continuously during sleep has the potential to overcome this limitation. OBJECTIVE: This study compares the diagnostic accuracy of these two temperatures for detecting ovulation and to investigate the correlation and agreement between these two temperatures in describing thermal changes in menstrual cycles. METHODS: This prospective study included 193 cycles (170 ovulatory and 23 anovulatory) collected from 57 healthy women. Participants wore a wearable device (Ava Fertility Tracker bracelet 2.0) that continuously measured the wrist skin temperature during sleep. Daily BBT was measured orally and immediately upon waking up using a computerized fertility tracker with a digital thermometer (Lady-Comp). An at-home luteinizing hormone test was used as the reference standard for ovulation. The diagnostic accuracy of using at least one temperature shift detected by the two temperatures in detecting ovulation was evaluated. For ovulatory cycles, repeated measures correlation was used to examine the correlation between the two temperatures, and mixed effect models were used to determine the agreement between the two temperature curves at different menstrual phases. RESULTS: Wrist skin temperature was more sensitive than BBT (sensitivity 0.62 vs 0.23; P<.001) and had a higher true-positive rate (54.9% vs 20.2%) for detecting ovulation; however, it also had a higher false-positive rate (8.8% vs 3.6%), resulting in lower specificity (0.26 vs 0.70; P=.002). The probability that ovulation occurred when at least one temperature shift was detected was 86.2% for wrist skin temperature and 84.8% for BBT. Both temperatures had low negative predictive values (8.8% for wrist skin temperature and 10.9% for BBT). Significant positive correlation between the two temperatures was only found in the follicular phase (rmcorr correlation coefficient=0.294; P=.001). Both temperatures increased during the postovulatory phase with a greater increase in the wrist skin temperature (range of increase: 0.50 °C vs 0.20 °C). During the menstrual phase, the wrist skin temperature exhibited a greater and more rapid decrease (from 36.13 °C to 35.80 °C) than BBT (from 36.31 °C to 36.27 °C). During the preovulatory phase, there were minimal changes in both temperatures and small variations in the estimated daily difference between the two temperatures, indicating an agreement between the two curves. CONCLUSIONS: For women interested in maximizing the chances of pregnancy, wrist skin temperature continuously measured during sleep is more sensitive than BBT for detecting ovulation. The difference in the diagnostic accuracy of these methods was likely attributed to the greater temperature increase in the postovulatory phase and greater temperature decrease during the menstrual phase for the wrist skin temperatures.

Impact of climate and public health interventions on the COVID-19 pandemic: a prospective cohort study.

BACKGROUND: It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). RESULTS: In univariate analyses, there were no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85-0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85-0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53-0.79), school closures (RRR 0.63, 95% CI 0.52-0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45-0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. INTERPRETATION: Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

Transcatheter aortic valve replacement in patients with concomitant mitral stenosis.

AIMS: Multivalvular disease is of increasing concern in elderly patients undergoing transcatheter aortic valve replacement (TAVR). The objective of the present analysis was to investigate the impact of concomitant mitral stenosis (MS) on clinical outcomes in patients undergoing TAVR for severe, symptomatic aortic stenosis (AS). METHODS AND RESULTS: Among 1339 patients undergoing TAVR between August 2007 and December 2015, adequate echocardiographic data for the assessment of severity and aetiology of MS was available in 971 (72.5%) patients. Patients were stratified according to degree and aetiology of concomitant MS. Mitral stenosis was documented in 176 (18.1%) TAVR patients (mean mitral valve area 1.9 ± 0.4 cm2) and considered degenerative in 110 (62.5%) and rheumatic in 66 (37.5%) patients, respectively. Mitral stenosis was categorized as moderate/severe in 28 patients (2.9%). Baseline characteristics were comparable between patients with vs. without MS. At 1 year, patients with MS were at increased risk of cardiovascular death [36 (21.4%) vs. 66 (8.7%); adjusted hazard ratio (HRadj) 3.64, 95% confidence interval (CI) 2.38-5.56] and disabling stroke [12 (7.1%) vs. 23 (3.0%); HRadj 2.98, 95% CI 1.46-6.09] as compared to patients without MS. Differences in cardiovascular death and disabling stroke emerged within 30 days of the index procedure and were largely driven by a difference in patients with rheumatic MS [cardiovascular death: 7 (10.6%) vs. 24 (3.2%), HRadj 4.80, 95% CI 1.98-11.6; disabling stroke: 4 (6.1%) vs. 16 (2.0%), HRadj 4.18, 95% CI 1.34-13.0]. CONCLUSION: Concomitant MS was documented in approximately one-fifth of patients undergoing TAVR for severe, symptomatic AS and associated with a three-fold increased risk of cardiovascular adverse events at 1 year. The difference emerged early and was largely driven by patients with rheumatic MS.

Association of acute kidney injury and bleeding events with mortality after radial or femoral access in patients with acute coronary syndrome undergoing invasive management: secondary analysis of a randomized clinical trial.

AIMS: In the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) trial, adults with acute coronary syndrome undergoing coronary intervention who were allocated to radial access had a lower risk of bleeding, acute kidney injury (AKI), and all-cause mortality, as compared with those allocated to femoral access. The mechanism of the mortality benefit of radial access remained unclear. METHODS AND RESULTS: We used multistate and competing risk models to determine the effects of radial and femoral access on bleeding, AKI and all-cause mortality in the MATRIX trial and to disentangle the relationship between these different types of events. There were large relative risk reductions in mortality for radial compared with femoral access for the transition from AKI to death [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.31-0.97] and for the pathway from coronary intervention to AKI to death (HR 0.49, 95% CI 0.26-0.92). Conversely, there was little evidence for a difference between radial and femoral groups for the transition from bleeding to death (HR 1.05, 95% CI 0.42-2.64) and the pathway from coronary intervention to bleeding to death (HR 0.84, 95% CI 0.28-2.49). CONCLUSION: The prevention of AKI appeared predominantly responsible for the mortality benefit of radial as compared with femoral access in the MATRIX trial. There was little evidence for an equally important, independent role of bleeding.

Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data.

Aims: To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions. Methods and results: We performed a systematic review and meta-analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5 years follow-up) and DANAMI-3-PRIMULTI (up to 4.7 years follow-up). After a median follow-up of 35 months (interquartile range 12-60 months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P = 0.02). The difference between groups was driven by MI. Conclusion: In this IPD meta-analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.

Radial versus femoral access and bivalirudin versus unfractionated heparin in invasively managed patients with acute coronary syndrome (MATRIX): final 1-year results of a multicentre, randomised controlled trial.

BACKGROUND: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. METHODS: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. FINDINGS: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90). INTERPRETATION: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. FUNDING: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

BACKGROUND: Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODS: We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTS: The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). CONCLUSIONS: In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Determinants of radiation dose during right transradial access: Insights from the RAD-MATRIX study.

BACKGROUND: The RAD-MATRIX trial reported a large operator radiation exposure variability in right radial percutaneous coronary procedures. The reasons of these differences are not well understood. Our aim was to appraise the determinants of operator radiation exposure during coronary right transradial procedures. METHODS: Patient arrangement during transradial intervention was investigated across operators involved in the RAD-MATRIX trial. Operator radiation exposure was analyzed according to the position of the patient right arm (close or far from the body) and in relation to the size of the upper leaded glass. RESULTS: Among the 14 operators who agreed to participate, there was a greater than 10-fold difference in radiation dose at thorax level (from 21.5 to 267 µSv) that persisted after normalization by dose-area product (from 0.35 to 3.5 µSv/Gy*cm2). Among the operators who positioned the instrumented right arm far from the body (110.4 µSv, interquartile range 71.5-146.5 µSv), thorax dose was greater than that in those who placed the instrumented arm close to the right leg (46.1 µSv, 31.3-56.8 µSv, P = .02). This difference persisted after normalization by dose-area product (P = .028). The use of a smaller full glass shield was also associated with a higher radiation exposure compared with a larger composite shield (147.5 and 60 µSv, respectively, P = .016). CONCLUSIONS: In the context of the biggest radiation study conducted in patients undergoing transradial catheterization, the instrumented right arm arrangement close to the leg and greater upper leaded shield dimensions were associated with a lower operator radiation exposure. Our findings emphasize the importance of implementing simple preventive measures to mitigate the extra risks of radiation exposure with right radial as compared with femoral access.

Radial versus femoral access in patients with acute coronary syndromes with or without ST-segment elevation.

Aims: To assess whether radial compared with femoral access is associated with consistent outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods and results: In the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) programme patients were randomized to radial or femoral access, stratified by STEMI (2001 radial, 2009 femoral) and NSTE-ACS (2196 radial, 2198 femoral). The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding In the overall study population, radial access reduced the NACE but not MACE endpoint at the prespecified 0.025 alpha. MACE occurred in 121 (6.1%) STEMI patients with radial access vs. 126 (6.3%) patients with femoral access [rate ratio (RR) = 0.96, 95% CI = 0.75-1.24; P = 0.76] and in 248 (11.3%) NSTE-ACS patients with radial access vs. 303 (13.9%) with femoral access (RR = 0.80, 95% CI = 0.67-0.96; P = 0.016) (Pint = 0.25). NACE occurred in 142 (7.2%) STEMI patients with radial access and in 165 (8.3%) patients with femoral access (RR = 0.86, 95% CI = 0.68-1.08; P = 0.18) and in 268 (12.2%) NSTE-ACS patients with radial access compared with 321 (14.7%) with femoral access (RR = 0.82, 95% CI = 0.69-0.97; P = 0.023) (Pint = 0.76). All-cause mortality and access site-actionable bleeding favoured radial access irrespective of ACS type (Pint = 0.11 and Pint = 0.36, respectively). Conclusion: Radial as compared with femoral access provided consistent benefit across the whole spectrum of patients with ACS, without evidence that type of presenting syndrome affected the results of the random access allocation.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND: It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS: We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS: We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION: In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING: The Medicines Company and Terumo.

Risk and timing of recurrent ischemic events among patients with stable ischemic heart disease, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction.

BACKGROUND: We aimed to compare differences in risk and timing of recurrent ischemic events among patients with stable ischemic heart disease (SIHD), non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS: We performed an individual data pooled analysis of 5 randomized controlled all-comer trials including a total of 8,859 patients and investigated the risk and timing of recurrent ischemic events among patients with SIHD (n = 3,543), NSTE-ACS (n = 3,364), and STEMI (n = 1,952) throughout 2 years of follow-up. RESULTS: At 2 years, all-cause mortality was higher among patients with STEMI (6.4%) and NSTE-ACS (6.1%) compared with those with SIHD (4.2%) (STEMI vs SIHD: hazard ratio [HR] 1.40, 95% CI 1.09-1.78, P = .007; NSTE-ACS vs SIHD: 1.40, 95% CI 1.13-1.73, P = .002). In a landmark analysis, the risk of mortality among patients with STEMI compared with those with SIHD was confined to the first 30 days after PCI (HR 6.19, 95% CI 3.15-12.16, P < .001) but was similar between 30 days and 2 years (HR 1.00, 95% CI 0.76-1.33, P = .974) (Pinteraction < .001). Conversely, patients with NSTE-ACS had a higher risk of mortality compared with those with SIHD both within the first 30 days (HR 2.19, 95% CI 1.08-4.47, P = .031) and beyond (HR 1.34, 95% CI 1.07-1.67, P = .012) (Pinteraction < .001). A similar pattern in the differential timing of events was observed for cardiac death. Beyond 30 days, the risk of myocardial infarction was comparable in patients with STEMI and SIHD, whereas the risk in patients with NSTE-ACS was increased (HR 1.65, 95% CI 1.23-2.21, P = .001). CONCLUSION: Whereas patients with NSTE-ACS are at increased risk for death at any time after PCI, the mortality of STEMI patients is higher during the first 30 days after PCI but not thereafter compared with patients with SIHD.

Effets du climat et des interventions de santé publique sur la pandémie de COVID-19 : une étude de cohorte prospective.

CONTEXTE: On ignore si les variations climatiques saisonnières, la fermeture des établissements scolaires ou d'autres interventions de santé publique entraîneront un ralentissement de la pandémie actuelle de maladie à coronavirus 2019 (COVID-19). Nous avons voulu déterminer si de façon globale la progression de l'épidémie est associée au climat ou aux interventions de santé publique visant à réduire la transmission du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). MÉTHODES: Nous avons procédé à une étude de cohorte prospective des 144 régions géopolitiques de la planète (375 609 cas) présentant au moins 10 cas de COVID-19, avec transmission locale, en date du 20 mars 2020, à l'exclusion de la Chine, de la Corée du Sud, de l'Iran et de l'Italie. Par analyse de régression à effets aléatoires pondérée, nous avons évalué le lien entre la progression de l'épidémie (exprimée sous forme de rapports de taux d'incidence [RTI] comparant les nombres cumulatifs de cas de COVID-19 du 27 mars 2020 à ceux du 20 mars 2020) avec les facteurs de latitude, température, humidité, fermeture des établissements scolaires, interdiction des grands rassemblements et mesures d'éloignement social qui étaient en place les 7 et 13 mars 2020 (période de 14 jours antérieure à l'évaluation). RÉSULTATS: Les analyses univariées ont révélé aucuns lien entre la progression de l'épidémie et les facteurs de latitude et de température, mais des liens négatifs faibles avec l'humidité relative (RTI par 10 %, 0,91, intervalle de confiance [IC] de 95 % 0,85­0,96) et l'humidité absolue (RTI par 5 g/m3 0,92, IC à 95 % 0,85­0,99). Des liens étroits ont été observés avec l'interdiction des grands rassemblements (RTI 0,65, IC à 95 % 0,53­0,79), la fermeture des établissements scolaires (RTI 0,63, IC à 95 % 0,52­0,78) et les mesures d'éloignement social (RTI 0,62, IC à 95 % 0,45­0,85). Dans un modèle multivarié, on a noté un lien étroit avec le nombre de mesures déployées par la santé publique (p pour tendance = 0,001), tandis que le lien avec l'humidité absolue s'atténuait. INTERPRÉTATION: La progression de l'épidémie de COVID-19 ne s'est pas révélée en lien avec la latitude ni avec la température, mais faiblement en lien avec l'humidité relative ou absolue. À l'inverse, les interventions de santé publique ont été étroitement associées à un ralentissement de la progression de l'épidémie.

Risk of Cardiac Arrhythmias Among Climbers on Mount Everest.

Importance: Arterial hypoxemia, electrolyte imbalances, and periodic breathing increase the vulnerability to cardiac arrhythmia at altitude. Objective: To explore the incidence of tachyarrhythmias and bradyarrhythmias in healthy individuals at high altitudes. Design, Setting, and Participants: This prospective cohort study involved healthy individuals at altitude (8849 m) on Mount Everest, Nepal. Recruitment occurred from January 25 to May 9, 2023, and data analysis took place from June to July 2023. Exposure: All study participants underwent 12-lead electrocardiogram, transthoracic echocardiography, and exercise stress testing before and ambulatory rhythm recording both before and during the expedition. Main Outcome: The incidence of a composite of supraventricular (>30 seconds) and ventricular (>3 beats) tachyarrhythmia and bradyarrhythmia (sinoatrial arrest, second- or third-degree atrioventricular block). Results: Of the 41 individuals recruited, 100% were male, and the mean (SD) age was 33.6 (8.9) years. On baseline investigations, there were no signs of exertional ischemia, wall motion abnormality, or cardiac arrhythmia in any of the participants. Among 34 individuals reaching basecamp at 5300 m, 32 participants climbed to 7900 m or higher, and 14 reached the summit of Mount Everest. A total of 45 primary end point-relevant events were recorded in 13 individuals (38.2%). Forty-three bradyarrhythmic events were documented in 13 individuals (38.2%) and 2 ventricular tachycardias in 2 individuals (5.9%). Nine arrhythmias (20%) in 5 participants occurred when climbers were using supplemental bottled oxygen, whereas 36 events (80%) in 11 participants occurred at lower altitudes when no supplemental bottled oxygen was used. The proportion of individuals with arrhythmia remained stable across levels of increasing altitude, while event rates per 24 hours numerically increased between 5300 m (0.16 per 24 hours) and 7300 m (0.37 per 24 hours) before decreasing again at higher altitudes, where supplemental oxygen was used. None of the study participants reported dizziness or syncope. Conclusion and Relevance: In this study, more than 1 in 3 healthy individuals experienced cardiac arrhythmia during the climb of Mount Everest, thereby confirming the association between exposure to high altitude and incidence of cardiac arrhythmia. Future studies should explore the potential implications of these rhythm disturbances.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.