What factors empower general practitioners for early cancer diagnosis? A 20-country European Delphi Study.

BACKGROUND: Some symptoms are recognised as red flags for cancer, causing the General Practitioner (GP) to refer the patient for investigation without delay. However, many early symptoms of cancer are vague and unspecific, and in these cases, a delay in referral risks a diagnosis of cancer that is too late. Empowering GPs in their management of patients that may have cancer is likely to lead to more timely cancer diagnoses. AIM: To identify the factors that affect European GPs' empowerment in making an early diagnosis of cancer. METHODS: This was a Delphi study involving GPs in 20 European countries. We presented GPs with 52 statements representing factors that could empower GPs to increase the number of early cancer diagnoses. Over three Delphi rounds, we asked GPs to indicate the clinical relevance of each statement on a Likert scale.The final list of statements indicated those that were considered by consensus to be the most relevant. RESULTS: In total, 53 GPs from 20 European countries completed the Delphi process, out of the 68 GPs who completed round one. Twelve statements satisfied the pre-defined criteria for relevance. Five of the statements related to screening and four to the primary/secondary care interface. The other selected statements concerned information technology (IT) and GPs' working conditions. Statements relating to training, skills and working efficiency were not considered priority areas. CONCLUSION: GPs consider that system factors relating to screening, the primary-secondary care interface, IT and their working conditions are key to enhancing their empowerment in patients that could have cancer. These findings provide the basis for seeking actions and policies that will support GPs in their efforts to achieve timely cancer diagnosis.

An RCT of Fecal Immunochemical Test Colorectal Cancer Screening in Veterans Without Recent Primary Care.

INTRODUCTION: The use of screening can prevent death from colorectal cancer, yet people without regular healthcare visits may not realize the benefits of this preventive intervention. The objective of this study was to determine the effectiveness of a mailed screening invitation or mailed fecal immunochemical test in increasing colorectal cancer screening uptake in veterans without recent primary care encounters. STUDY DESIGN: Three-arm pragmatic randomized trial. SETTING/PARTICIPANTS: Participants were screening-eligible veterans aged 50-75 years, without a recent primary care visit who accessed medical services at the Corporal Michael J. Crescenz Veteran Affairs Medical Center between January 1, 2017, and July 31, 2017. All data were analyzed from March 1, 2018, to July 31, 2018. INTERVENTION: Participants were randomized to (1) usual opportunistic screening during a healthcare visit (n=260), (2) mailed invitation to screen and reminder phone calls (n=261), or (3) mailed fecal immunochemical test outreach plus reminder calls (n=61). MAIN OUTCOME MEASURES: The main outcome under investigation was the completion of colorectal cancer screening within 6 months after randomization. RESULTS: Of 782 participants in the trial, 53.9% were aged 60-75 years and 59.7% were African American. The screening rate was higher in the mailed fecal immunochemical test group (26.1%) compared with usual care (5.8%) (rate difference=20.3%, 95% CI=14.3%, 26.3%; RR=4.52, 95% CI=2.7, 7.7) or screening invitation (7.7%) (rate difference=18.4%, 95% CI=12.2%, 24.6%; RR=3.4, 95% CI=2.1, 5.4). Screening completion rates were similar between invitation and usual care (rate difference=1.9%, 95% CI= -2.4%, 6.2%; RR=1.3, 95% CI=0.7, 2.5). CONCLUSIONS: Mailed fecal immunochemical test screening promotes colorectal cancer screening participation among veterans without a recent primary care encounter. Despite the addition of reminder calls, an invitation letter was no more effective in screening participation than screening during outpatient appointments. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT02584998.

Anaphylaxis-induced atrial fibrillation and anesthesia: Pathophysiologic and therapeutic considerations.

Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been correlated to autoimmune system activation as it is the underlying mechanism of persistent atrial fibrillation development. Current research supports an association between the complement system activation and lymphocyte-pro-inflammatory cytokines release with the cardiac conduction system and atrial fibrosis. The loss of CD28 antigen from CD4+ CD28+ T lymphocytes seems to play a major role in atrial fibrillation development and prognosis. Except atrial fibrillation, a variety of additional electrocardiographic changes, resembling those with digitalis intoxication may accompany anaphylaxis and particularly Kounis syndrome. Histamine is one well-known mediator in allergic and inflammatory conditions as physiologically regulates several cardiovascular and endothelial functions with arrhythmogenic potential. The increased oxidative stress, measured by the redox potentials of glutathione, has been correlated with atrial fibrillation incidence and prevalence. The use of antazoline, a first-generation antihistamine agent used for rapid conversion of recent-onset atrial fibrillation in patients with preserved left ventricular function and for rapid atrial fibrillation termination during accessory pathway ablation denotes that anaphylaxis-induced histamine production could be the cause of atrial fibrillation at least in some instances. The anaphylaxis diagnosis in anesthesia can be challenging owing to the absence of cutaneous manifestetions such as flushing, urticaria, or angioedema. Anticoagulation for stroke prevention, rate and rhythm control medications, invasive methods such as radiofrequency ablation or cryoablation of pulmonary veins as well surgical ablation constitute the treatment basis of atrial fibrillation. Understanding the underlying mechanisms of atrial fibrillation by cardiologists, anesthesiologists and surgeons, as well as potential treatments, to optimize care is of paramount importance.

Kounis Syndrome­not a Single-organ Arterial Disorder but a Multisystem and Multidisciplinary Disease

Coronary symptoms associated with conditions related to mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, further inducing allergic, hypersensitivity, anaphylactic, or anaphylactic insults, are currently referred to as the Kounis syndrome. Kounis syndrome is caused by inflammatory mediators released during allergic insults, post-inflammatory cell activation, and interactions via multidirectional stimuli. A platelet subset of 20% with high- and low-affinity IgE surface receptors is also involved in this process. Kounis syndrome is not just a single-organ but also a complex multisystem and multi-organ arterial clinical condition; it affects the coronary, mesenteric, and cerebral arteries and is accompanied by allergy­hypersensitivity­anaphylaxis involving the skin, respiratory, and vascular systems in the context of anesthesia, surgery, radiology, oncology, or even dental and psychiatric medicine; further, it has significantly influences both morbidity and mortality. Kounis syndrome might be caused by numerous and continuously increasing causes, with broad clinical symptoms and signs, via multi-organ arterial system involvement, in patients of any age, thereby demonstrating predominant anaphylactic features in terms of a wide spectrum of mast cell-association disorders. Cardiac symptoms, such as chest pain, coronary vasospasm, angina pectoris, myocardial infarction, stent thrombosis, acute cardiac failure, and sudden cardiac death associated with subclinical, clinical, acute, or chronic allergic reactions, constitute the clinical manifestations of this syndrome. Since its first description, a common pathway between allergic and non-allergic coronary events has been demonstrated. The hypothesis is based on the existence of a much higher degree of mast cell degranulation at plaque erosion or rupture sites compared with at the adjacent areas or even more distant segments in post-acute myocardial infarction of non-allergic etiology. Although mast cell activation, differentiation, and mediator release takes days or weeks, the mast cell degranulation may occur just before any acute coronary event, further resulting in coronary artery vasoconstriction and atheromatous plaque rupture. It seems that medications and natural molecules stabilizing the mast cell membrane as well as monoclonal antibodies protecting the mast cell surface can emerge as novel therapeutic modalities for acute coronary and cerebrovascular event prevention.

Financial incentives for completion of fecal occult blood tests among veterans: a 2-stage, pragmatic, cluster, randomized, controlled trial.

BACKGROUND: Rates of patient completion of fecal occult blood tests (FOBTs) are often low. OBJECTIVE: To examine whether financial incentives increase rates of FOBT completion. DESIGN: A 2-stage, parallel-design, pragmatic, cluster, randomized, controlled trial with clustering by clinic day (ClinicalTrials.gov: NCT01516489). SETTING: Primary care clinic of the Philadelphia Veterans Affairs Medical Center. PATIENTS: 1549 patients who were prescribed an FOBT (unique samples of 713 patients for stage 1 and 836 patients for stage 2). INTERVENTION: In stage 1, patients were assigned to usual care or receipt of $5, $10, or $20 for FOBT completion. In stage 2, different patients were assigned to usual care or receipt of $5, a 1 in 10 chance of $50, or entry into a $500 raffle for FOBT completion. MEASUREMENTS: Primary outcome was FOBT completion within 30 days. Preplanned subgroup analyses examined 30-day FOBT completion by previous nonadherence to a prescribed FOBT. RESULTS: In stage 1, none of the incentives increased rates of FOBT completion. In stage 2, a 1 in 10 chance of $50 increased FOBT completion compared with usual care (between-group difference, 19.6% [95% CI, 10.7% to 28.6%]; P < 0.001) but a $5 fixed payment and entry into a raffle for $500 did not. None of the incentives were more effective among patients who had previously been nonadherent to an FOBT than among patients who had previously completed an FOBT. LIMITATIONS: Single Veterans Affairs medical center setting, short follow-up, use of 3-sample rather than 1-sample immunochemical FOBTs, limited power to detect small effects of incentives, inability to evaluate cost-effectiveness. CONCLUSION: A 1 in 10 chance of receiving $50 was effective at increasing rates of FOBT completion, but 5 other tested incentives were not. PRIMARY FUNDING SOURCE: Veterans Affairs Center for Health Equity Research and Promotion.

Warfarin: what are the clinical implications of an out-of-range-therapeutic international normalized ratio?

Warfarin is a commonly used oral anticoagulant, and has well-established clinical efficacy. However, it has a narrow therapeutic window, and a mode-of-action affected by inter-individual differences and environmental factors. The effectiveness and safety of warfarin are closely related to maintenance of the international normalized ratio (INR) within therapeutic range. A supra-therapeutic INR puts patients at risk of bleeding, whereas a sub-therapeutic INR may not protect against thromboembolic complications. Research suggests a lack of anticoagulation control during warfarin therapy in different settings. Careful monitoring of the INR is essential, especially in geriatric or cancer populations who are at an increased risk of major hemorrhage. Warfarin is an effective treatment but optimization of the risk-benefit ratio is crucial in order to maximize efficacy and safety. Here, we will assess the extent to which INRs are an issue in the management of warfarin therapy, and the effect INRs may have on clinical outcomes.