Response to Adamson et al. (2020): 'Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: Outcomes from a specialist clinic in the UK'.

In a paper published in the Journal of the Royal Society of Medicine, Adamson et al. (2020) interpret data as showing that cognitive behavioural therapy leads to improvement in patients with chronic fatigue syndrome and chronic fatigue. Their research is undermined by several methodological limitations, including: (a) sampling ambiguity; (b) weak measurement; (c) survivor bias; (d) missing data and (e) lack of a control group. Unacknowledged sample attrition renders statements in the published Abstract misleading with regard to points of fact. That the paper was approved by peer reviewers and editors illustrates how non-rigorous editorial processes contribute to systematic publication bias.

Quantitative Flow Ratio to Predict Nontarget Vessel-Related Events at 5 Years in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Angiography-Guided Revascularization.

Background In ST-segment-elevation myocardial infarction, angiography-based complete revascularization is superior to culprit-lesion-only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator-free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST-segment-elevation myocardial infarction undergoing angiography-guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2-dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST-segment-elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54-11.83], P<0.001), driven by higher rates of nontarget vessel myocardial infarction (12.8% versus 3.1%, respectively; HR, 4.38 [95% CI, 1.47-13.02], P=0.008) and nontarget vessel revascularization (58.6% versus 7.7%, respectively; HR, 10.99 [95% CI, 6.39-18.91], P<0.001) with no significant differences for cardiac death. Multivariable analysis identified QFR ≤0.80 but not ≥50% DS by 3-dimensional quantitative coronary angiography as an independent predictor of the primary end point. Results were consistent, including only >30% DS by 3-dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography-guided percutaneous coronary intervention for nonculprit lesions among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The concept of 'illness without disease' impedes understanding of chronic fatigue syndrome: a response to Sharpe and Greco.

In a recent article in Medical Humanities, Sharpe and Greco characterise myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an 'illness without disease', citing the absence of identified diagnostic markers. They attribute patients' rejection of psychological and behavioural interventions, such as cognitive-behavioural therapy (CBT) and graded exercise therapy (GET), to a 'paradox' resulting from a supposed failure to acknowledge that 'there is no good objective evidence of bodily disease'. In response, we explain that understandings about the causes of and treatments for medical complaints have shifted across centuries, and that conditions once thought to be 'psychosomatic' have later been determined to have physiological causes. We also note that Sharpe and Greco do not disclose that leading scientists and physicians believe that ME/CFS is a biomedical disease, and that numerous experts, not just patients, have rejected the research underlying the CBT/GET treatment approach. In conclusion, we remind investigators that medical classifications are always subject to revision based on subsequent research, and we therefore call for more humility before declaring categorically that patients are experiencing 'illness without disease'.

For LGBTQ Patients, High-Quality Care In A Welcoming Environment.

Outside major urban centers, LGBTQ patients often travel hours to find trusted clinicians. One Iowa clinic has created a safe space just down the road.

First in Switzerland: concomitant off-pump transapical transcatheter aortic valve implantation and mitral valve reconstruction with the NeoChord system.

Old and polymorbid patients with multivalvular heart disease comprise a special patient group, with high perioperative morbidity and mortality. We report the case of an 80-year-old, female, polymorbid patient with severe mitral valve regurgitation and moderate to severe aortic valve stenosis. This is the first case in Switzerland of a concomitant transapical transcatheter aortic valve implantation and mitral valve reconstruction with the NeoChord system, on a beating heart and with a minimally invasive approach through a left anterolateral thoracotomy. This case emphasises the possibility of a low-risk minimally invasive procedure on this high-risk patient-group and shows the importance of interdisciplinary discussion and cooperation in heart teams for optimal patient treatment.

Five-Year Outcomes in Patients With Diabetes Mellitus Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents.

Background The choice of optimal drug-eluting stent therapy for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remains uncertain. We aimed to assess the long-term clinical outcomes after percutaneous coronary intervention with biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES) in patients with DM. Methods and Results In a prespecified subgroup analysis of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization) trial (NCT01443104), patients randomly assigned to ultrathin-strut BP-SES or thin-strut DP-EES were stratified according to diabetic status. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, at 5 years. Among 2119 patients, 486 (22.9%) presented with DM. Compared with individuals without DM, patients with DM were older and had a greater baseline cardiac risk profile. In patients with DM, target lesion failure at 5 years occurred in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (risk ratio, 1.23; 95% CI, 0.87-1.73 [P=0.24]). In individuals without DM, target lesion failure at 5 years occurred in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (risk ratio, 0.98; 95% CI, 0.77-1.26 [P=0.90; P for interaction=0.31]). Cumulative 5-year incidence rates of cardiac death, target vessel myocardial infarction, clinically indicated target lesion revascularization, and definite stent thrombosis were similar among patients with DM treated with BP-SES or DP-EES. There was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusions In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout 5 years between patients with DM treated with ultrathin-strut BP-SES or thin-strut DP-EES. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01443104.

Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT.

BACKGROUND: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence. METHODS: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole. RESULTS: On the original protocol-specified primary outcome measure - overall improvement rates - there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years. CONCLUSIONS: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Rehospitalizations Following Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction: Results From a Multi-Center Randomized Trial.

BACKGROUND: Rehospitalizations (RHs) after ST-elevation myocardial infarction carry a high economic burden and may deteriorate quality of life. Characterizing patients at higher risk may allow the design of preventive measures. We studied the frequency, reasons, and predictors for unplanned cardiac and noncardiac RHs in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: In this post-hoc analysis of the COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction; NCT00962416) trial including 1137 patients, unplanned cardiac and noncardiac RHs occurred in 133 (11.7%) and in 79 patients (6.9%), respectively, at 1 year. The most frequent reasons for unplanned cardiac RHs were recurrent chest pain without evidence of ischemia (20.4%), recurrent chest pain with ischemia and coronary intervention (16.9%), and ischemic events (16.9%). Unplanned noncardiac RHs occurred most frequently attributed to bleeding (24.5%), infections (14.3%), and cancer (9.1%). On multivariate analysis, left ventricular ejection fraction (22% increase in the rate of RHs per 10% decrease; P=0.03) and angiographic myocardial infarction Syntax score (34% increase per 10-point increase; P=0.01) were independent predictors of unplanned cardiac RHs. Age emerged as the only independent predictor of unplanned noncardiac RHs. Regional differences for unplanned cardiac RHs were observed. CONCLUSIONS: Among ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention in the setting of a randomized, clinical trial, unplanned cardiac RHs occurred in 12% with recurrent chest pain being the foremost reason. Unplanned noncardiac RHs occurred in 7% with bleeding as the leading cause. Left ventricular ejection fraction and Syntax score were independent predictors of unplanned cardiac RHs and identified patient subgroups in need for improved secondary prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962416.

Once again, the PACE authors respond to concerns with empty answers.

In their response to Geraghty, the PACE investigators state that they have "repeatedly addressed" the various methodological concerns raised about the trial. While this is true, these responses have repeatedly failed to provide satisfactory explanations for the trial's very serious flaws. This commentary examines how the current response once again demonstrates the ways in which the investigators avoid acknowledging the obvious problems with PACE and offer non-answers instead-arguments that fall apart quickly under scrutiny.

Impact of Patient and Lesion Complexity on Long-Term Outcomes Following Coronary Revascularization With New-Generation Drug-Eluting Stents.

Long-term clinical outcomes of new-generation drug-eluting stents in complex anatomic and clinical settings are not well defined. This study assessed the impact of patient and lesion complexity on 2-year outcomes after coronary revascularization with ultrathin strut biodegradable-polymer (BP) sirolimus-eluting stents (SES) versus durable-polymer (DP) everolimus-eluting stents (EES). In a prespecified analysis of the BIOSCIENCE randomized trial (NCT01443104), complex patients (911 of 2,119; 43%) were defined by the presence of acute ST-elevation myocardial infarction (MI); left ventricular ejection fraction ≤30%; renal dysfunction; insulin-treated diabetes; treatment of ostial lesion, bypass graft, unprotected left main lesion; or 3-vessel intervention. The primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization. At 2 years, complex compared with simple patients had a greater risk of TLF (14.5% vs 7.4%, risk ratio 2.05, 95% confidence interval 1.56 to 2.69; p <0.001). The difference was sustained beyond 1 year on landmark analysis. Complex patients had higher rates of the patient-oriented composite end point of death, any MI, or any revascularization (23% vs 14.4%; p <0.001) as well as definite stent thrombosis (1.6% vs 0.4%, p = 0.006). There were no differences in TLF and patient-oriented composite end point between the BP-SES versus DP-EES, consistently among simple and complex patients. In conclusion, patient and lesion complexity had a durable adverse impact on clinical outcomes throughout 2 years of follow-up in this all-comers randomized trial. Safety and efficacy of new-generation BP-SES and DP-EES were comparable, irrespective of complexity status.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES: The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND: Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS: Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS: Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS: This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Clinical outcomes according to diabetic status in patients treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: prespecified subgroup analysis of the BIOSCIENCE trial.

BACKGROUND: Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus. METHODS AND RESULTS: BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27-2.56; P=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67-2.10; P=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58-1.33; P=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49-3.41; P=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39-1.25; P=0.23, in nondiabetics). CONCLUSIONS: In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Giant coronary artery fistula complicated by cardiac tamponade.

A 30 year old female was admitted to the hospital with cardiogenic shock due to cardiac tamponade. A ruptured giant coronary artery fistula (CAF) originating from the left main coronary artery draining into the right atrium was identified as the cause. In this case report we describe the clinical course with emphasis on diagnostic work-up and imaging.

Randomized comparison of a titanium-nitride-oxide-coated stent with a stainless steel stent for coronary revascularization: the TiNOX trial.

BACKGROUND: Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide-coated stents compared with stainless steel stents. METHODS AND RESULTS: Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide-coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55+/-0.63 versus 0.90+/-0.76 mm, P=0.03) and percent diameter stenosis (26+/-17% versus 36+/-24%, P=0.04) in lesions treated with titanium-nitride oxide-coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide-coated stent group (P=0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide-coated stents than in control stents (18+/-21 versus 48+/-28 mm3, P<0.0001). Major adverse cardiac events at 6 months were less frequent in titanium-nitride-oxide-coated stents than in control stent-treated patients (7% versus 27%, P=0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P=0.07). CONCLUSIONS: Revascularization with titanium-nitride-oxide-coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide-coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.

Hemodynamic effects of endobronchial application of ornipressin versus terlipressin.

BACKGROUND: Ornipressin and terlipressin, two ADH-derivates, are instilled endobronchially for bronchoscopy- related bleeding without sufficient evidence of efficacy, nor safety. OBJECTIVES: To compare the immediate hemodynamic effects of ornipressin and terlipressin used for procedure-related bleeding during flexible bronchoscopy. METHODS: This retrospective study included patients referred for flexible bronchoscopy who needed administration of ornipressin (15 patients) or terlipressin (15 patients) for procedure-related bleeding. Endobronchial ornipressin (5 IU) or terlipressin (0.5 mg) was administered through the bronchoscope when bleeding persisted for 2 min of continuous suction, or when bleeding was considered increasing in time or major. Hemodynamic data were collected before, during and after administration of either drug. RESULTS: Biopsy-associated hemoptysis requiring medical treatment occurred in 110 (4.2%) of 2,592 bronchoscopies. After administration of ornipressin, no significant change in heart rate or blood pressure was observed. Following terlipressin instillation, heart rate increased from 93 +/- 17 to 101 +/- 22 b.p.m. (p = 0.03), and blood pressure decreased from 107 +/- 14 to 101 +/- 17 mm Hg (p = 0.04). Oxygen saturation under supplemental nasal oxygen was not different in both groups. None of the 110 patients died from bronchoscopy-related hemoptysis or needed further intervention to stop bleeding or prolonged monitoring because of hemodynamic instability. CONCLUSIONS: In contrast to ornipressin, administration of terlipressin is associated with significant changes in heart rate and blood pressure. However, these changes are of minor clinical importance, and terlipressin can be safely given for bronchoscopy-associated bleeding.