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BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.
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Objective: To determine the relationship between pre-existent hyperglycemia among patients with COVID-19 pneumonia requiring oxygen supplementation. Study Design: Cross-sectional study Place and Duration of Study: COVID-19 isolation wards, High Dependency Units, and Intensive Care Units of Mayo Hospital Lahore Pakistan, from Apr to May 2021. Methodology: Eighty-one patients with hyperglycemia but without a prior diagnosis of diabetes mellitus were selected for this study. The data was collected from COVID PCR positive patients admitted to the isolation ward and intensive care unit at Mayo Hospital, Lahore. All the patients admitted during a 2-month duration from April to May 2021. Results: A Total of 81 patients were included, of which 54(66.7%) were males. On the basis of HbA1c, 68(84%), 12(14.8%) and 1 (1.2%) patient(s) were diagnosed diabetic, pre-diabetic and non-diabetic respectively. Of the four patients requiring mechanical ventilation, 3(75%) were diabetic, and 1(25%) was pre-diabetic. Of patients who required non-invasive ventilation, 68(84.4%), 12(14.2%) and 1(1.3%) were diabetic, pre-diabetic and non-diabetic, respectively. Conclusion: There is a significant burden of undiagnosed diabetes mellitus and pre-diabetes among patients with severe COVID-19 who require oxygen supplementation or admission to high-dependency units. Therefore, all patients should undergo thorough testing to exclude underlying diabetes mellitus.
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49 Table 1Exercise Prescription template using the FITT-VP (frequency, intensity, type, time, volume and progress) principle of exercise prescription.Exercise type Frequency (per week) Intensity Time (mins/session) Volume (weekly mins) Progression As always if you develop any concerning symptoms during exercise please stop and seek medical advice 49 Table 2‘How do I estimate exercise intensity?’ patient guide as part of the exercise prescription template and patient information leafletIntensity RPE (Rating of perceived exertion) % of HR max** Talk test 0 Resting 1 2 Very light No noticeable change in breathing or sweating Low 3 Somewhat light <55% Can talk and sing 4 Light Moderate 5 Somewhat moderate 55–74% Can talk, can’t sing Increased breathing and sweating 6 Moderate 7 Somewhat hard Feeling ‘out of breath’ and increased sweating High 8 Very hard 75–90% Can’t talk or sing 9 Extremely hard 10 Maximal exertion **%HR max will not be an accurate measure of exercise intensity if your heart rate is effected by certain medications or conditions 49 Figure 1Levels of self reported physical activity based on the NAPQ-short questionnaire and WHO 2020 physical activity guidelines[Figure omitted. See PDF] 49 Figure 2Variety of patients with a diagnosis of a cardiac condition or a family history of a cardiac condition receiving an exercise prescription. HCM;hypertrophic cardiomyopathy, DCM;dilated cardiomyopathy, ARVC;arrhythmogenic right ventricular cardiomyopathy, LQTS;long QT syndrome, Brugada;brugada Syndrome, CPVT;catecholaminergic polymorphic ventricular tachycardia, SADS;sudden adult death syndrome, Other;Friedreich’s ataxia, ischemic heart disease, supraventricular tachycardia)[Figure omitted. See PDF]ConclusionsCompared to the general adult Irish population, self reported adherence to the WHO PA Guidelines was 6% lower among the CRY Clinic patient cohort (33% vs. 27%). Additionally, reported resistance exercise levels was lower (30%) than aerobic exercise (72%). This is despite resistance exercise being additionally beneficial for many cardiac conditions. During the period of data collection, access to gyms and group exercise was limited due to pandemic government restrictions that likely effected resistance exercise more than aerobic exercise. In fact, a significant increase in recreational walking during covid restrictions was previously reported. Exercise is often discussed during medical consultation but rarely prescribed. In our cohort only 0.5% of patients received an Ex Rx. The reported barriers to Ex Rx are lack of time, perceived lack of patient engagement, complex co-morbidities and clinician education. Attempts were made in the form of education and resource provision to clinicians to challenge perceived barriers. Ex Rx are important in the CRY Clinic not only for the known benefits of PA but as inappropriate exercise can be harmful for some cardiac conditions. The Ex Rx enabled the benefit of PA to be gained by the safe promotion of appropriate exercise to such patients (figure 2). The introduction of this PA assessment and Ex Rx was a successful call to action to incorporate exercise as medicine to the CRY Clinic. ‘Walking is a (wo)mans best medicine’ (Hippocrates 460BC).
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Continued investment in the rural primary care workforce will be key to improving access issues. disparities in cancer outcomes between rural and urban populations remain a global problem.1 Australia is not excepted to such rural-urban inequities.2 For breast cancer, women living in rural New South Wales (NSW) have worse survival rates compared with their urban counterparts.3'4 They are also more likely to have late-stage breast cancer upon diagnosis, longer diagnostic interval and higher risk of death.5-7 Improved cancer control to reduce rural-urban disparities rightly remains an important health priority. Numerous qualitative studies have investigated what influences help-seeking behaviour for such women across various international settings.10-18 A meta-ethnographic synthesis of these studies revealed eight common concepts that affected help-seeking behaviour: symptom detection, initial symptom interpretation, symptom monitoring, social interactions, emotional interactions, priority of seeking medical help, appraisal of health services and personal-environmental factors.19 However, these qualitative findings must be interpreted within the contexts that they were conducted in, considering related social and cultural issues for that sample group. The relationship between prolonged breast cancer pathways and poorer survival is well established,22 and identifying factors that prolong the patient interval and determining whether these factors are more common in rural areas could help facilitate the identification of targeted interventions to address the gaps in service delivery and reduce the disparity in breast cancer outcomes for people living in rural Australia. Overview of themes Six key themes emerged from the data analysis, each encompassing a range of facilitators and barriers to help-seeking: 1) Initial symptom appraisal;2) symptom monitoring processes;3) emotions and attitudes towards symptoms;4) social interactions;5) personal or environmental factors;and 6) accessing GP services.
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Little is known about the risk of hypertension and type 2 diabetes in relation to changes in frequency and amount of alcohol consumption. This study investigated associations between changes in alcohol consumption and the risk of both conditions. This study included 96,129 individuals without hypertension and/or diabetes mellitus aged ≥ 20 years between 2006 and 2008, with follow-up until 31 December 2015. This study identified 29,043 and 18,784 incident cases of hypertension and type 2 diabetes, respectively, during an average follow-up period of 6.2 ± 2.6 and 6.9 ± 1.9 years. This study measured changes in frequency and amount of alcohol consumption using standardized self-administered questionnaires over approximately 2 years. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for the respective risks of the two conditions. Repeated occasional or frequent binge drinking was associated with an increased risk of hypertension (HR: 1.16 or 1.32;95% CI: 1.11, 1.21 or 1.16, 1.51) and type 2 diabetes (HR: 1.14 or 1.36;95% CI: 1.09, 1.20 or 1.17, 1.58) compared with continuous nondrinking. Reductions as well as increases in frequency of alcohol consumption among binge drinkers were associated with higher hypertension (HR: 1.29 or 1.30;95% CI: 1.11, 1.49 or 1.13, 1.49) and type 2 diabetes (HR: 1.26 or 1.56;95% CI: 1.06, 1.49 or 1.34, 1.81) risk. This study demonstrated that repeated binge drinking, even with a reduction of weekly alcohol consumption frequency, was associated with a higher risk of hypertension and type 2 diabetes.
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Clinical Commentary Children and adolescents who regularly participate in sports have a lower risk of obesity, chronic disease, alcohol and drug use, and criminal activity, and have higher self-esteem compared with nonparticipants.1–3 However, only 24% of youth engage in the 60 minutes of physical activity per day recommended by national guidelines.4 Participation in structured sports has decreased from 45% to 38% in the past 10 years, and children in low-income households are one-half as likely to participate regularly in sports compared with children from higher-income households.4 The Aspen Institute found growing disparities in physical activity by income;the percentage of inactive children in households with annual incomes less than $25,000 increased from 24% in 2012 to 33% in 2018, whereas the percentage of inactive children in households earning more than $100,000 decreased from 14% to 9.9% during the same time frame.4 In the United States, 49 states and the District of Columbia require a preparticipation physical evaluation before participation in school sports (Vermont leaves the decision to screen to individual school districts).5 The major components of the preparticipation physical evaluation are a detailed family history, medical history, symptom history, and physical examination.6,7 Concern about undiagnosed cardiac disease in athletes has grown over the past several decades following high-profile cases of sudden cardiac death.8 Rates of sudden cardiac death in young athletes range from 0.4 to 4 per 100,000 athlete-years.8,9 One suggested role of the preparticipation physical evaluation is preventing these deaths through early identification of children at high risk. Israel implemented mandatory preparticipation physical evaluations with ECGs and exercise stress testing in 1997, but sudden cardiac death rates have not changed.19 When studied in the United States, preparticipation physical evaluation with or without an ECG did not significantly predict or reduce sudden cardiac death.9 Most athletes in the Football Association (England, soccer) with cardiac death had normal screening results despite mandatory preparticipation physical evaluations, ECGs, and echocardiography.20 Preparticipation physical evaluation with an ECG has a high false-positive rate (40%) and false-negative rate overall (4% to 5%), with both preparticipation evaluations and ECGs having higher false-negative rates specifically for hypertrophic cardiomyopathy (10%).11,21,22 A cost analysis showed that implementing preparticipation physical evaluations with ECGs in the United States would cost $470 per athlete per year or $51 billion to $69 billion over 20 years.23 Sudden cardiac death in an athlete is rare, totaling fewer than 100 deaths per year in the United States, at a rate of 1 in 150,000 athletes per year.8,9 In Denmark, the rate of sudden cardiac death in the general population is more than 20 times greater than the rate in teenaged and young adult athletes (0.43 to 0.47 per 100,000 athlete person-years).24 The preintervention rate in the Veneto study (4 per 100,000 athlete-years) was much higher than that observed in more contemporary studies. Considering the lower rates of sudden cardiac death in the United States, even if the benefit in the Veneto study could be replicated, the number of ECGs needed to prevent one sudden cardiac death would be 33,000 to 192,000.23 An estimated 2% of children are disqualified from sports participation through the screening process when it includes an ECG.22 Approximately 45 million children and adolescents participate in sports in the United States;therefore, 900,000 children and adolescents would be unable to participate in organized physical activity without clear evidence of benefit if universal ECG screening were recommended.25 Intensive exercise commonly causes cardiac remodeling, termed athlete’s heart, that can lead to asymptomatic bradyarrhythmia, first-degree heart block, and ventricular hypertrophy.25 ECG and echocardiogram changes can be mistaken for concerning pathology, prompting unnecessary testing. Screening patients at high risk during well-child examinations may be underused, regardless of sports participation;one survey of pediatricians found that 24% had never ordered an ECG.28 Notably, rates of sudden cardiac death are equivalent or lower in athletes compared with nonathletes.12,13,23 Emergency response plans that include training staff in resuscitation and use of an automated external defibrillator are recommended and have been shown to save lives.29–31 In an eight-year follow-up study of professional soccer players who screened negative for cardiac risk, three athletes experienced cardiac arrest during competition or training, and all of them were successfully resuscitated.32 TAKE-HOME MESSAGES FOR RIGHT CARE Screening for undiagnosed cardiac disease during well-child examinations using a validated tool such as the American Heart Association 14-element evaluation is a high-value, low-cost intervention for children and adolescents regardless of sports participation.
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According to her mother, the patient had no fever, upper respiratory symptoms, abdominal pain, vomiting, diarrhea, discolored urine, blood in stool, change in gait, weakness, or joint swelling. The results, completed 3 days after initial presentation, were the following: О Uric acid: 3.5 mg/dL (normal, 2.6-6.4 mg/dL) О LDH: 198 units/L (normal, 220-462 units/L) О CRP: 3.1 mg/L О M pneumoniae antibodies, IgM: 1234 U/mL (normal, < 770 U/mL) О Mpneumoniae antibodies, IgG: < 0.90 (normal < 0.90) О QuantiFERON-TB Gold: negative Differential diagnosis The initial differential diagnosis included several infectious and noninfectious etiologies that could account for the findings of the patient's skin lesions and laboratory results (Box). Erythema nodosum can be the first sign of a systemic illness such as tuberculosis and other bacterial or fungal infections, inflammatory bowel disease, sarcoidosis, or cancer, although in many cases, no cause of EN can be found.1,3-7 The most common cause of EN in children is idiopathic, followed by infection, sarcoidosis, and use of antibiotic drugs.1,6,8 Among infectious etiologies of EN in children, the most common are streptococcal pharyngitis, Yersinia, Mycoplasma, Chlamydia, histoplasmosis, coccidioidomycosis, and MycobacteriumA6-8 Diagnostic evaluation of EN includes a comprehensive history and physical exam as well as a complete blood cell count with differential, ESR, and CRP level.1,3 An individual patient's presentation might warrant further evaluation, including testing for streptococcal infection, chest ra- diography, stool cultures, or testing for infection with tuberculosis.1 Although EN is often self-limited, any identified underlying disorder should be treated appropriately. [...]a negative family history of irritable bowel disease and lack of gastrointestinal disturbances pointed away from Crohn disease or ulcerative colitis as possible etiologies.