Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial.

Background: Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity. Methods: TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands. Individuals ≥60 years, fully vaccinated against COVID-19 were eligible for participation and randomized into one of four study groups: 1) 0.5 ml influenza vaccination Vaxigrip Tetra followed by 0.3 ml BNT162b2 COVID-19 booster vaccination 21 days later, (2) COVID-19 booster vaccination followed by influenza vaccination, (3) influenza vaccination concurrent with the COVID-19 booster vaccination, and (4) COVID-19 booster vaccination only (reference group). Primary outcome was the geometric mean concentration (GMC) of IgG against the spike (S)-protein of the SARS-CoV-2 virus, 21 days after booster vaccination. We performed a non-inferiority analysis of concurrent administration compared to booster vaccines alone with a predefined non-inferiority margin of -0.3 on the log10-scale. Findings: 154 individuals participated from October, 4, 2021, until November, 5, 2021. Anti-S IgG GMCs for the co-administration and reference group were 1684 BAU/ml and 2435 BAU/ml, respectively. Concurrent vaccination did not meet the criteria for non-inferiority (estimate -0.1791, 95% CI -0.3680 to -0.009831) and antibodies showed significantly lower neutralization capacity compared to the reference group. Reported side-effects were mild and did not differ between study groups. Interpretation: Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this. Trial registration number: EudraCT: 2021-002186-17. Funding: The study was supported by the ZonMw COVID-19 Programme.

Gap balanced adjusted mechanical alignment versus measured resection mechanical alignment: a randomised controlled trial.

INTRODUCTION: Alignment goals in total knee replacement (TKR) is a topical subject. This study compares the short-term functional outcomes and patient reported outcome measures (PROMs) of two philosophies for knee arthroplasty alignment: measured resection (MR) and an individualised alignment philosophy, with the tibia mechanically aligned and an instrumented gap balancer (GB) to align the femur in both flexion and extension. PATIENTS AND METHODS: 94 knees were enrolled in this randomised controlled trial. The surgical protocol used a MR technique for mechanical alignment or a GB technique for individualised alignment. Primary outcome was quadriceps strength. Secondary outcomes included validated functional tests and PROMs as well as patient satisfaction. Outcomes were assessed pre-operatively, at 6 weeks, 3, 6 and 12 months post-operatively. RESULTS: At 12-month follow-up, there was no significant difference in the change from baseline mean quadriceps peak torque between the two groups (p = 0.988). Significant improvement in the change in range of motion (ROM) in the GB group compared to the MR group at 3 months (13° vs 6° p = 0.028) but this improvement was not significant at 1 year (20° vs 17° p = 0.21). The functional test of balance showed statistically significant improvement at 6 weeks (p = 0.03) in the GB group but this difference was not maintained. PROMs favoured the GB group, with the KOOS pain scoring statistically better (p ≤ 0.05) at 6 weeks, 3, 6 and 12 months. CONCLUSIONS: Individualised alignment philosophy utilising a GB technique did not demonstrate an improvement in the primary outcome measure quadriceps peak torque. Improvement was seen in the GB group in PROM pain scores that was significant, both statistically and clinically, out to at least 1 year. Gains that were seen in functional assessment with GB, although significant at some time points, were no longer significant at 1 year and no difference was seen in quads strength. Compared to a MR technique, the individualised GB technique appears to confer some improvement in pain, ROM and some functional tests following TKR in the short-term.

Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial.

PURPOSE: To investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma. METHODS: In cohort 6 of the multicohort, open-label, phase I/II CheckMate 040 study, patients who were treatment-naive, sorafenib-intolerant, or had progressed on sorafenib were randomly assigned 1:1 to nivolumab 240 mg once every 2 weeks plus cabozantinib 40 mg once daily (doublet arm); or nivolumab 3 mg/kg every 2 weeks plus cabozantinib 40 mg once daily with ipilimumab 1 mg/kg once every 6 weeks (triplet arm). Primary objectives were safety and tolerability, objective response rate, and duration of response by investigator assessment per RECIST v1.1. Secondary objectives included progression-free survival (by blinded independent central review) and overall survival. RESULTS: Seventy-one patients were randomly assigned: 36 to the doublet arm and 35 to the triplet arm. After 32.0-month median follow-up, objective response rate (95% CI) was 17% (6 to 33) and 29% (15 to 46) in the doublet and triplet arms, respectively. Median (95% CI) duration of response was 8.3 (6.9 to not estimable) months in the doublet arm and not reached (0.0 to not estimable) in the triplet arm. Median progression-free survival was 5.1 and 4.3 months, and median overall survival was 20.2 and 22.1 months for the doublet and triplet arms, respectively. Grade 3-4 treatment-related adverse events occurred in 50% and 74% of patients and treatment-related adverse events leading to discontinuation were reported for 11% and 23% in the doublet and triplet arms, respectively. There were no treatment-related deaths in either arm. CONCLUSION: Nivolumab plus cabozantinib with or without ipilimumab showed encouraging preliminary antitumor activity and had consistent safety profiles with those established for the individual drugs in patients with advanced hepatocellular carcinoma.

A split-face comparative performance evaluation of injectable hyaluronic acid-based preparations HCC and CPM-HA20G in healthy females.

INTRODUCTION: Skin revitalizers are used for skin quality improvement purposes. Hyaluronan hybrid cooperative complexes (HCC, Profhilo®, IBSA Pharmaceuticals) are an anti-aging treatment with a large amount of pure hyaluronic acid (HA) based on stable, cooperative, and hybrid complexes. Cohesive polydensified matrix Hyaluronic Acid (CPM-HA20, Belotero Revive®, Merz Pharmaceuticals GmbH) is a slightly cross-linked HA (20 mg/ml) with glycerol (17.5 mg/ml). AIMS: To evaluate the performance of HCC and CPM-HA20G for skin quality improvement in healthy female subjects. METHODS: This was a split-face, single-blinded study that enrolled 24 healthy female subjects. Injections were given on three separate occasions. HCC was injected on the right cheek, while CPM-HA20G was injected on the left cheek. A battery of skin property measurements was used to evaluate the skin. Skin properties and overall satisfaction were analyzed using mixed models with the values at baseline, at week 1, week 8, and week 14 as an outcome and a random effect of subject and fixed effects of treatment, visit, and the treatment by visit interaction. RESULTS: Both products showed evidence of effect relative to baseline on surface hydration (AU), elasticity (N/m) TEWL (g/m2 h), and melanin (AU). CPM-HA20G also showed significant evidence of effect relative to baseline on water content (%), and HCC on pore count (n) and hemoglobin (AU). Satisfaction reported by the subjects themselves showed positive trends of satisfaction over time for multiple skin properties. There were no significant differences between the tested products in the observed skin characteristics over time. CONCLUSION: These devices are effective and safe treatments for skin quality improvement, especially moisturization, with high patient satisfaction and generally mild and transient side effects.

Outcomes after Flow Diverter Treatment in Subarachnoid Hemorrhage: A Meta-Analysis and Development of a Clinical Prediction Model (OUTFLOW).

BACKGROUND: patients with a subarachnoid hemorrhage (SAH) might need a flow diverter (FD) placement for complex acutely ruptured intracranial aneurysms (IAs). We conducted a meta-analysis and developed a prediction model to estimate the favorable clinical outcome after the FD treatment in acutely ruptured IAs. METHODS: a systematic literature search was performed from 2010 to January 2021 in PubMed and Embase databases. Studies with more than five patients treated with FDs within fifteen days were included. In total, 1157 studies were identified. The primary outcome measure was the favorable clinical outcome (mRS 0-2). Secondary outcome measures were complete occlusion rates, aneurysm rebleeding, permanent neurologic deficit caused by procedure-related complications, and all-cause mortality. A prediction model was constructed using individual patient-level data. RESULTS: 26 retrospective studies with 357 patients and 368 aneurysms were included. The pooled rates of the favorable clinical outcome, mortality, and complete aneurysm occlusion were 73.7% (95% CI 64.7-81.0), 17.1% (95% CI 13.3-21.8), and 85.6% (95% CI 80.4-89.6), respectively. Rebleeding occurred in 3% of aneurysms (11/368). The c-statistic of the final model was 0.83 (95% CI 0.76-0.89). All the studies provided a very low quality of evidence. CONCLUSIONS: FD treatment can be considered for complex ruptured IAs. Despite high complication rates, the pooled clinical outcomes seem favorable. The prediction model needs to be validated by larger prospective studies before clinical application.

NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: Insight from the On-TIME II trial.

BACKGROUND: N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NT-proBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI). METHODS: we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI. RESULTS: Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR <70% had higher NT-proBNP values compared to patients with complete STR (>70%) [Mean ±SD 375.2 ±1021.7 vs 1007.4 ±2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), P <.001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR <70%) were: NT-proBNP (OR 1.17, 95%CI 1.04-1.31, P = .009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, P = .013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, P <.001), time to intervention (OR 1.06, 95%CI 1.01-1.11, P = .021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, P = .022). CONCLUSIONS: In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reperfusion, supporting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients.

Impact of elevated HbA1c on long-term mortality in patients presenting with acute myocardial infarction in daily clinical practice: insights from a 'real world' prospective registry of the Zwolle Myocardial Infarction Study Group.

BACKGROUND: Long-term clinical outcome is less well known in up to presentation persons unknown with diabetes mellitus who present with acute myocardial infarction and elevated glycosylated haemoglobin (HbA1c) levels on admission. We aimed to study the prognostic impact of deranged HbA1c at presentation on long-term mortality in patients not known with diabetes, presenting with acute myocardial infarction. METHODS: A single-centre, large, prospective observational study in patients with and without known diabetes admitted to our hospital for ST-segment elevation myocardial infarction (STEMI) and non-STEMI. Newly diagnosed diabetes mellitus was defined as HbA1c of 48 mmol/l or greater and pre-diabetes mellitus was defined as HbA1c between 39 and 47 mmol/l. The primary endpoint was all-cause mortality at short (30 days) and long-term (median 52 months) follow-up. RESULTS: Out of 7900 acute myocardial infarction patients studied, 1314 patients (17%) were known diabetes patients. Of the 6586 patients without known diabetes, 3977 (60%) had no diabetes, 2259 (34%) had pre-diabetes and 350 (5%) had newly diagnosed diabetes based on HbA1c on admission. Both short-term (3.9% vs. 7.4% vs. 6.0%, p<0.001) and long-term mortality (19% vs. 26% vs. 35%, p<0.001) for both pre-diabetes patients as well as newly diagnosed diabetes patients was poor and comparable to known diabetes patients. After multivariate analysis, newly diagnosed diabetes was independently associated with long-term mortality (hazard ratio 1.72, 95% confidence interval 1.27-2.34, P=0.001). CONCLUSIONS: In the largest study to date, newly diagnosed or pre-diabetes was present in 33% of acute myocardial infarction patients and was associated with poor long-term clinical outcome. Newly diagnosed diabetes (HbA1c ⩾48 mmol/mol) is an independent predictor of long-term mortality. More attention to early detection of diabetic status and initiation of blood glucose-lowering treatment is necessary.

Plasma Viscosity Has a Role in the Diagnosis of Prosthetic Joint Infection After Total Knee Arthroplasty.

BACKGROUND: The diagnosis of prosthetic joint infection (PJI) is challenging because no single test has consistently demonstrated an adequate discriminative potential. The combination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with adequate thresholds is well established. This study sought to investigate the role of plasma viscosity (PV) in the diagnosis of PJI following painful total knee arthroplasty. METHODS: The medical notes, and hematological and microbiology results of 310 patients who underwent revision for a painful total knee arthroplasty were evaluated. Infection was confirmed using Musculoskeletal Infection Society criteria in 102 patients (32.9%), whereas 208 patients (67.1%) were classified as noninfected. Serum investigations including ESR, CRP, and PV were analyzed using receiver observer curves and optimal cutoff points identified. RESULTS: There was a strong correlation between PV and both ESR and CRP. The area under curve was 0.814 for PV and 0.812 for ESR. Statistical analysis showed noninferiority of PV as compared to ESR in diagnosing PJI. A PV value of ≥ 1.81 mPa.s. had the best efficiency of 82.1%. Combining a CRP ≥ 13.5 mg/L with a PV ≥ 1.81 mPa.s. in a serial test approach yielded the highest specificity of 97.9% and positive likelihood ratio of 22.8. Sensitivity was 47.9% and a negative likelihood ratio of 0.53. CONCLUSION: PV is noninferior to ESR in diagnosing PJI. Its use is justified in clinical practice. It is cheaper, quicker, more efficient, and not influenced by hematocrit levels or medication. In this cohort, a PV value ≥ 1.81 mPa.s. would be an adequate cutoff to diagnose PJI in combination with CRP ≥ 13.5 mg/L.

Effect of early tirofiban administration on N-terminal pro-B-type natriuretic peptide level in patients treated with primary percutaneous coronary intervention.

OBJECTIVES: To investigate the potential association between early tirofiban treatment and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after primary percutaneous coronary intervention (PCI). BACKGROUND: Whether the use of adjunctive early glycoprotein IIb/IIIa inhibitors (GPIs) therapy, may affect the level of NT-proBNP after primary PCI is poorly studied. METHODS: Nine hundred and eighty four ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI were randomized to either pre-hospital tirofiban administration or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hr after PCI. RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post-PCI. Post-PCI NT-proBNP level dichotomized with median value as cut-off (968.8 pg/mL, IQR 430.9-1970.0) was significantly lower in patients treated with early tirofiban as compared to placebo (45.5% vs. 54.2% P = 0.011). At multivariate logistic regression analysis, independent predictors of post-PCI NT-proBNP level above the median were: NT-proBNP baseline level (OR 5.19; 95% CI, 2.92-9.25, P < 0.001), Killip class>I (OR 4.07; 95% CI 1.24-13.36, P = 0.021), anterior infarct location (OR 2.61; 95% CI 1.84-3.70, P < 0.001), age (years) (OR 1.04; 95% CI 1.03-1.06, P < 0.001), male gender (OR 0.38; 95% CI 0.26-0.57, P < 0.001), prior PCI (OR 0.49; 95% CI 0.27-0.90, P = 0.021) and tirofiban administration (OR 0.71; 95% CI 0.51-0.99; P = 0.045). CONCLUSIONS: In a large cohort of STEMI patients, pre-hospital tirofiban administration was independently associate with a lower risk of high NT-proBNP level after primary PCI, supporting the potential benefit of early antithrombotic treatment administration in STEMI patients. The trial is registered under No. ISRCTN06195297.

Dental implants with fixed prosthodontics in oligodontia: A retrospective cohort study with a follow-up of up to 25 years.

STATEMENT OF PROBLEM: Long-term assessments of implant survival and treatment outcome in patients with oligodontia are lacking. PURPOSE: The purpose of this retrospective clinical study was to assess which factors determine a long-term implant survival and treatment outcome of up to 25 years in a cohort of patients with oligodontia. MATERIAL AND METHODS: The medical records of all patients with oligodontia treated with fixed implant prosthodontics between January 1991 and December 2015 in the Department of Oral and Maxillofacial Surgery at the University Medical Center Groningen, the Netherlands, were assessed. Specifically, this involved the retrieval of records on the need for and mode of bone augmentation, implant survival, and survival of and adverse events associated with the prosthodontics. The Kaplan-Meier estimator was used to analyze implant and superstructure survival. Log-rank tests were used to compare the survival of subgroups. RESULTS: A total of 126 patients with oligodontia were treated with dental implants. Of the 777 implants in total, 56 were lost, resulting in a 5-year cumulative survival of 95.7% (95% confidence interval [CI], 94.2% to 97.2%) and a 10-year cumulative survival of 89.2% (95% CI, 86.2% to 92.2%). The survival of implants placed in regions where bone augmentation surgery had been performed was significantly lower. The 5-year cumulative superstructure survival was 90.5% (95% CI, 87.6% to 93.5%), and the 10-year cumulative superstructure survival was 80.3% (95% CI, 75.3% to 85.3%). The performance of the screw-retained and cemented superstructures was comparable, but the survival of single crowns was significantly higher than the survival of fixed partial dentures (P<.001). CONCLUSIONS: Implant treatment is a predictable treatment option for patients with oligodontia with a favorable long-term outcome. Survival of implants in augmented areas is lower.

Factors associated with deferred lesion failure following fractional flow reserve assessment in patients with diabetes mellitus.

OBJECTIVE: To explore the predictors of deferred lesion failure (DLF) in patients with diabetes mellitus (DM) and lesions with a fractional flow reserve (FFR) >0.80 and to examine whether a predictive relationship between negative FFR values (>0.80-1.00) and DLF exists. BACKGROUND: DM is associated with rapidly progressive atherosclerosis and predictors of DLF in FFR negative lesions in this high-risk group are unknown. METHODS: All DM patients who underwent FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/7/2015. Patients carrying ≥1 FFR negative lesion(s) were assessed for DLF, and multivariate models used to identify independent factors associated with DLF. RESULTS: A total of 205 patients with 252 FFR >0.80 lesions were identified. At a mean follow-up of 3.1 ± 1.4 years, DLF occurred in 29/205 (14.1%) patients, 31/252 (12.3%) lesions. Using marginal Cox regression multivariate analysis, insulin requiring DM [HR 2.24 (95%CI; 1.01-4.95), P = 0.046] and prior revascularization [HR 2.70 (95%CI 1.21-6.01), P = 0.015] were identified as being associated with a higher incidence of DLF. Absolute FFR values in FFR negative lesions in DM patients are not predictive of DLF (receiver operating characteristics curve analysis: area under the curve: 0.57 ± 0.06, 95%CI 0.46-0.69). CONCLUSIONS: In DM patients with FFR negative lesions, insulin requiring DM and prior revascularization are predictors for DLF. In contrast to non-DM patients, no predictive relationship between absolute negative FFR values (ranging >0.80-1.00) and the risk of DLF exists in DM patients. © 2017 Wiley Periodicals, Inc.

Randomised comparison of drug-eluting versus bare-metal stenting in patients with non-ST elevation myocardial infarction.

OBJECTIVE: The superiority of drug-eluting stents (DES) over bare-metal stents (BMS) in patients with ST elevation myocardial infarction (STEMI) is well studied; however, randomised data in patients with non-ST elevation myocardial infarction (NSTEMI) are lacking. The objective of this study was to investigate whether stenting with everolimus-eluting stents (EES) safely reduces restenosis in patients with NSTEMI as compared to BMS. METHODS: ELISA-3 patients were asked to participate in the angiographic substudy and were randomised to DE (Xience V) or BM (Vision) stenting (ELISA-3 group). The primary end point was minimal luminal diameter (MLD) at 9-month follow-up angiography. In addition, 296 patients with NSTEMI who were excluded or did not want to participate in the ELISA-3 trial (RELI group) were randomised to DE or BM stenting and underwent clinical follow-up only (major adverse cardiac events (MACE), stent thrombosis (ST)). A pooled analysis was performed to assess an effect on clinical outcome. RESULTS: 178 of 540 ELISA-3 patients participated in the angiographic substudy. MLD at 9 months angiography was 2.37±0.63 mm (DES) versus 1.84±0.62 mm (BMS), p<0.001. Binary restenosis occurred in 1.9% in the DES group versus 16.7% in the BMS group (RR 0.11, 95% CI 0.02 to 0.84, p=0.007). In the pooled analysis, the incidence of MACE, target vessel revascularisation and ST at 2 years follow-up in the DES versus BMS group was 12.5% versus 16.0% (p=0.28), 4.0% versus 10.4% (p=0.009) and 1.3% versus 3.0% (p=0.34), respectively. CONCLUSIONS: In patients with NSTEMI, use of EES is safe and decreases both angiographic and clinical restenosis as compared to BMS http://www.isrctn.com/search?q=39230163. TRIAL REGISTRATION NUMBER: 39230163; Post-results.

Fractional Flow Reserve-Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus.

To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)-guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with ≥1 remaining FFR-negative (>0.80) medically treated lesions [FFR(-)MT] and those with only FFR-positive lesions (≤0.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(-)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 ± 18.1 months, FFR(-)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p = 0.02, Cox regression-adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI was a strong effect modifier within the FFR(-)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM, particularly those with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis.

Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus.

OBJECTIVE: Deferred revascularisation based upon fractional flow reserve (FFR >0.80) is associated with a low incidence of target lesion failure (TLF). Whether deferred revascularisation is also as safe in diabetes mellitus (DM) patients is unknown. METHODS: All DM patients and the next consecutive Non-DM patients who underwent a FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/07/2015. Patients with lesions FFR >0.80 were analysed according to the presence vs. absence of DM, while patients who underwent index revascularisation in FFR-assessed or other lesions were excluded. The primary endpoint was the incidence of TLF; a composite of target lesion revascularisation (TLR) and target vessel myocardial infarction (TVMI). RESULTS: A total of 250 patients (122 DM, 128 non-DM) who underwent deferred revascularisation of all lesions (FFR >0.80) were compared. At a mean follow up of 39.8 ± 16.3 months, DM patients compared to non-DM had a higher TLF rate, 18.1 vs 7.5 %, logrank p ≤ 0.01, Cox regression-adjusted HR 3.65 (95 % CI 1.40-9.53, p < 0.01), which was largely driven by a higher incidence of TLR (17.2 vs. 7.5 %, HR 3.52, 95 % CI 1.34-9.30, p = 0.01), whilst a non-significant but numerically higher incidence of TVMI (6.1 vs. 2.0 %, HR 3.34, 95 % CI 0.64-17.30, p = 0.15) was observed. CONCLUSIONS: This study, the largest to directly compare the clinical outcomes of FFR-guided deferred revascularisation in patients with and without DM, shows that DM patients are associated with a significantly higher TLF rate. Whether intravascular imaging, additional invasive haemodynamics or stringent risk factor modification may impact on this higher TLF rate remains unknown.

The effect of thrombus aspiration during primary percutaneous coronary intervention on clinical outcome in daily clinical practice.

It was the purpose of this study to assess the effect of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) on reperfusion and clinical outcome in a real-world STEMI population. The decision to use TA (Export catheter, Medtronic) was at the discretion of the treating cardiologist. The primary endpoint was mortality at short (in-hospital) and long term (one year) follow-up. Secondary end points were post-PCI TIMI flow, residual ST deviation and enzymatic infarct size. Cox proportional hazard models (propensity-weighted) and logistic regression analysis were used to adjust for known covariates, associated with mortality. We performed a retrospective analysis of prospectively collected data on 2,552 consecutive PPCI-treated STEMI patients between 2007 and 2010. Use of TA increased from 6.9% in 2007 to 62.2% in 2010 (p<0.001). TA was performed in 899 patients (35.2%). In-hospital and one-year mortality rates were 3.0% and 6.0%, respectively, in the TA group and 3.5% and 7.6% in the no-TA group. After multivariate analysis, TA was not significantly associated with in-hospital mortality (adjusted odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.33-1.49, p=0.36) nor one year mortality (adjusted hazard ratio [HR]: 0.75, 95%CI: 0.47-1.20, p=0.23) or cardiac mortality (HR: 0.81; 95%CI: 0.45-1.46, p=0.49). After matching on the propensity score, the HR in the TA group for one year mortality was 0.70 (95%CI: 0.41-1.20, p=0.19) and for one-year cardiac mortality 0.70 (95%CI: 0.36-1.34, p=0.28). In conclusion, no significant relationship of TA with one of the secondary end points was found. The use of TA increased over the last years but clinical outcome was similar in both groups (TA vs no-TA) in this large cohort of real-world, unselected STEMI patients.

Adherence to monthly online self-assessments for short-term monitoring: a 1-year study in relapsing-remitting multiple sclerosis patients after start of disease modifying treatment.

BACKGROUND: The participation of neurologists and patients in studies on the effectiveness and safety of newly authorized drugs in multiple sclerosis (MS) is insufficient. Monthly online self-assessments using patient-reported outcomes may help in short-term monitoring of neurological changes and side effects. OBJECTIVE: Investigate in relapsing-remitting (RR) MS patients the adherence to monthly online self-assessments after the start of disease modifying treatment. METHODS: Observational study in 39 neurological departments in The Netherlands. Patients starting glatiramer acetate treatment were instructed to complete online the Modified Fatigue Impact Scale 5-item version and the 8-item Leeds Multiple Sclerosis Quality of Life scale every month during 1 year (T0 toT12). RESULTS: Sixty-three investigators included 163 analyzable patients. At T3, 148 (90.8%) patients had completed all questionnaires; at T6, 142 (87.1%); at T9, 133 (81.6%); and at T12, 123 (75.5%). Eight (4.9%) patients did not complete any questionnaire. Median values for inter-assessment intervals ranged from 32 to 34 days (first quartile [Q1] 30 days, third quartile [Q3] 41 days), and the final assessment was at 417 days (median: Q1 385 days, Q3 480 days). Forty-three (26.3%) patients completed the questionnaires at all time points (completion adherent) with their final assessment within 30 days after the scheduled T12 (interval adherent). Eighty (49.1%) patients were completion adherent, but not interval adherent. Forty (24.5%) patients were not completion adherent, as they discontinued assessments prematurely. Men were more interval adherent than women (47.5% vs 20.0%; P = 0.001). CONCLUSION: The observation that three out of four (75.5%) RRMS patients completed two short questionnaires at all monthly time points during 1 year after the start of disease modifying treatment suggests that intensive online monitoring in this patient group is feasible. As only one in five (19.6%) patients adhered to the time intervals between self-assessments, measures are needed that improve the timely completion of questionnaires.

Are antibiotics related to oral combination contraceptive failures in the Netherlands? A case-crossover study.

PURPOSE: To investigate whether there is an association between use of antibiotics and breakthrough pregnancy. METHODS: The study was performed in a population-based prescription database (IADB.nl). We computed case-crossover odds ratios of 397 cases of defined breakthrough pregnancy comparing the use of antibiotics in the exposure window with the use of antibiotics in two control windows. We defined a control group consisting of 29 022 other pregnancies. We computed case-control odds ratios of the use of antibiotics in cases as compared with controls in the different time windows. RESULTS: The case-crossover odds ratios comparing the use of antibiotics in the exposure window with both control windows were 2.21 (95%CI = 1.03-4.75) and 1.65 (95%CI = 0.78-3.48), respectively. The traditional case-control odds ratios after adjustment for age were 1.71 (95%CI = 1.09-2.66) in the exposure window, 0.81 (95%CI = 0.44-1.47) 2 months before the exposure window, and 1.04 (95%CI = 0.61-1.78) 12 months before the exposure window. CONCLUSIONS: We did find a relationship between the use of antibiotics and breakthrough pregnancy in a population-based prescription database. The results did not hold for broad-spectrum antibiotics or in a sensitivity analysis. The results are partly not the same as those found in a pharmacoepidemiological study with a similar design using two US pregnancy databases. Both studies can suffer from bias and confounding, but these will be different because of the use of different databases.

Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay.

AIMS: To evaluate the impact of longer duration of pre-hospital initiated antiplatelet and antithrombotic therapy on outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In this sub-analysis of the Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial, we studied, in 1,370 patients, the effect of pre-treatment time (time from administering study medication to time of angiography) on complete ST-segment resolution (STR), initial patency and 30-day mortality. Study medication consisted of high dose tirofiban (HDT) or control (placebo or no HDT) on top of high dose clopidogrel, aspirin and unfractionated heparin. Median pre-treatment time was 55 min (44-70). Longer pre-treatment was associated with longer transportation times, longer in-hospital delay, longer total ischaemic time (all p<0.001) and higher 30-day mortality (3.6% vs. 1.8%, p=0.046). Longer HDT pre-treatment time was independently associated with increased complete STR both before (odds ratio [OR] 1.51, 95%; confidence interval [CI] 0.98-2.32; p=0.06) and after PCI (OR 1.43, 95%; CI 1.02-2.02; p=0.039) and with a significantly improved initial TIMI 2 or 3 flow (51.4% vs. 43.4%, p=0.042) and reduced 30-day mortality (2.1% vs. 5.0%, p=0.047) as compared to longer control pre-treatment. CONCLUSIONS: Longer time delay before primary PCI is associated with increased mortality. Pre-treatment with high dose tirofiban, however, may compensate for this negative effect by improving ST-segment resolution and initial patency and by reducing mortality. Further studies should be performed to confirm that this is an attractive therapy for patients with longer delays to reperfusion.

Job satisfaction and short sickness absence due to the common cold.

OBJECTIVE: This study investigated whether short episodes of sickness absence were associated with job satisfaction. PARTICIPANTS: 199 wage earners who reported sick due to the common cold between January 2003 and April 2003. METHODS: Job satisfaction was assessed on the first day of sickness absence and associated with the duration of sickness absence using a multiple logistic regression model to which demographics, working conditions, and the week day on which sick-leave was taken were stepwise added as covariates. RESULTS: Workers with low job satisfaction scores had higher odds (odds ratio [OR] =3.85; 95% confidence interval [CI] 1.74 to 8.51) of being > 3 days absent from work due to the common cold compared to satisfied workers. However, the duration of sickness absence due to the common cold was more strongly related to the day of taking sick-leave with workers who reported sick on Monday or Tuesday being longer absent (OR=5.36; 95% CI 1.44 to 9.90) than those who reported sick on Friday. CONCLUSIONS: When having a common cold, dissatisfied workers are longer absent from work although the duration of short episodes of sickness absence seems to be determined by the week day on which sick-leave is taken rather than working conditions or perceptions about work.