Strenuous Activity Research Articles

Painful Plantar Rash with Systemic Symptoms

Painful Plantar Rash with Systemic Symptoms

Rhabdomyolysis Following Ad26.COV2.S COVID-19 Vaccination.

We report the case of a 19-year-old male who complained of myalgia, muscle weakness, and darkened urine two days after receiving his Ad26.COV2.S (Johnson & Johnson, New Brunswick, New Jersey, United States) COVID-19 vaccination. Blood examination revealed an increased creatine kinase (CK) level, and his urinary dipstick tested positive for blood, indicative of acute rhabdomyolysis. Serum creatinine levels were normal. Rhabdomyolysis due to strenuous physical activity was ruled out and further diagnostics excluded an autoimmune cause. Under repeated treatment with intravenous fluid resuscitation (outpatient treatment), his symptoms resolved and peak CK levels of 44,180 U/L returned to almost normal levels within two weeks. Rhabdomyolysis is a rare, potentially fatal vaccine-induced reaction. Further research is needed to better understand the underlying pathomechanism and to investigate whether subcutaneous injection of vaccines may be able to prevent rhabdomyolysis.

Compression Garments Reduce Soft Tissue Vibrations and Muscle Activations during Drop Jumps: An Accelerometry Evaluation.

Objectives: To explore the effects of wearing compression garments on joint mechanics, soft tissue vibration and muscle activities during drop jumps. Methods: Twelve healthy male athletes were recruited to execute drop jumps from heights of 30, 45 and 60 cm whilst wearing compression shorts (CS) and control shorts (CON). Sagittal plane kinematics, ground reaction forces, accelerations of the quadriceps femoris (QF), hamstrings (HM) and shoe heel-cup, and electromyography images of the rectus femoris (RF) and biceps femoris (BF) were collected. Results: Compared with wearing CON, wearing CS significantly reduced the QF peak acceleration at 45 and 60 cm and the HM peak acceleration at 30 cm. Wearing CS significantly increased the damping coefficient for QF and HM at 60 cm compared with wearing CON. Moreover, the peak transmissibility when wearing CS was significantly lower than that when wearing CON for all soft tissue compartments and heights, except for QF at 30 cm. Wearing CS reduced the RF activity during the pre-, post-, and eccentric activations for all heights and concentric activations at 45 cm; it also reduced the BF activity during post- and eccentric activations at 30 and 60 cm, respectively. The hip and knee joint moments and power or jump height were unaffected by the garment type. Conclusion: Applying external compression can reduce soft tissue vibrations without compromising neuromuscular performance during strenuous physical activities that involve exposure to impact-induced vibrations.

Analysis of ST-elevation myocardial infarction occurring in soldiers during strenous military training

BackgroundAt our tertiary care cardiology center, we are receiving soldiers who sustained acute ST-Elevation Myocardial Infarction (STEMI) during the strenuous Battle Field Efficiency Test (BPET) and other such activities. MethodsThis was a single-center observational study to assimilate and analyze the precipitating causes, risk factors, symptoms, and the efficacy of the management protocols in soldiers sustaining STEMI during the BPET or other forms of strenuous military training. ResultsAll 25 soldiers with documented STEMI following strenuous military training presented with chest pain as the primary symptom. 88% had symptoms either during or within 1st hour of the strenuous activity. 76% underwent thrombolysis with an angiographic success rate of 95%. Primary PCI was possible in only 3/25 (12%) of the cases, of which 2 (66%) did not require stenting after thrombus aspiration; 88% of soldiers reported “training for the event” for less than four times/week. ConclusionSTEMI precipitated by strenuous unaccustomed military training have exclusively single vessel affection with an excellent response to thrombolysis and thrombus aspiration. Thus, the timely institution of pharmacological or mechanical revascularization therapy has dramatic results in the preservation of ventricular function. The lack of training for the strenuous event provides strong evidence for comprehensive, graded, physical training prior to strenuous military activities to prevent acute coronary syndromes.

The role of psycho-oncologic screenings in the detection and evaluation of depression in head and neck cancer aftercare patients

PurposeCancer and morbidity during a therapeutic regimen can result in somatic and psychiatric impairment. We have evaluated the need of appropriate psychological screening by analyzing a large collective of head and neck cancer (HNC) patients with particularly burdensome symptoms.MethodsHNC-aftercare patients were asked about somatic and psychological symptoms by means of standardized questionnaires of the European Organization for Research and Treatment of Cancer (EORTC Q30 and QLQ-H&N35). Patients with poor well-being values on the World Health Organization-5-Well-Being Index were screened for depression by using the Mini International Neuropsychiatric Interview, and adequate treatment was initiated, if necessary.ResultsOur sample consisted of 453 HNC-aftercare patients (average age 64.5 years; 72.0% male; 28.0% female). 25.1% showed abnormalities based on their WHO-5 questionnaire. A current major depressive episode was observed in 8.5% of the total study group. Patients with lip and oral cavity tumors showed the highest depression prevalence (18.9%). Time since initial HNC diagnosis showed no clear trend with regard to the number of depression cases. 50.0% of patients with a current major depressive episode consented to receiving assistance and/or therapy. Within the total study population, the most burdensome symptoms were found to be “dry mouth” (48.3%), “trouble doing strenuous activities” (46.0%), “trouble taking a long walk” (38.5%), and “worry” (35.5%). Aftercare patients with a depression diagnosis tended to have heavier symptom burdens than people without major depression.ConclusionsDespite the various cancer-related burdensome factors, prevalence levels of depression among the HNC-aftercare patients and the general population were similar. Nevertheless, since the number of diagnosed depression cases is high, the need for psychological treatment should be considered within the tumor collective. Furthermore, screening for depression should be implemented in clinical routines by using the appropriate standardized questionnaires.

Midwives and protection of pregnant workers in Western Switzerland: Practices, difficulties and contributions

BackgroundSwitzerland's maternity protection legislation aims to protect the health of pregnant employees and their unborn children by regulating their potential occupational exposure to hazards and strenuous activities. This legislation provides a role for obstetricians, but not for midwives. AimsIdentify the practices of Switzerland's French-speaking midwives that favour the implementation of maternity protection legislation and reflect on the profession's role in supporting pregnant employees. Methods356 midwives answered an online questionnaire. The analysis focuses on the 205 midwives who perform pregnancy consultations in their practice. Data were analysed in two stages using STATA software: 1) simple descriptive and correlational statistics and 2) hierarchical cluster analysis to identify typologies of practices by grouping similar responses. FindingsDespite having no officially defined role in Switzerland's maternity protection legislation, its midwives actively participate in protecting pregnant employees , especially those with more knowledge of the legislation, those with more years of experience and those practicing independently. The barriers that midwives face when trying to provide greater support for pregnant employees are linked significantly to their lack of knowledge about the legislation, a lack of recognition for their role in the current legislation and a lack of continuing education about the occupational health risks associated with pregnancy at work. Conclusions and implications for practiceTheir profession and specific practices give midwives privileged access to pregnant employees. Midwives' knowledge of the legislation, their awareness of the occupational risks and hazards facing pregnant employees and the conviction that their profession has the potential to make a difference could all be improved. The role of midwives should be—and deserves to be—formally and legally recognised and integrated into Switzerland's maternity protection legislation.

Impact Of Activity Monitoring On Physical Activity, Sedentary Behavior, And Weight During The Covid-19 Pandemic

Emerging evidence has reported decreases in individuals’ physical activity and increases in sedentary behavior and bodyweight during the COVID-19 pandemic. The present study sought to assess the ability of physical activity monitoring to mitigate these negative outcomes. Such devices may promote physical activity and discourage sedentary behavior by providing feedback to the users. Therefore, individuals who do not use physical activity monitoring may report greater pandemic-related reductions in physical activity and greater increases in sedentary behavior and bodyweight relative to individuals who use monitors. PURPOSE: To assess the ability of physical activity monitoring to moderate potential changes in physical activity, sedentary behavior, and bodyweight due to the COVID-19 pandemic. METHODS: A sample of adults from a public, American university (N = 404, 40.3 ± 15.3 years old) completed an online survey consisting of validated questionnaires assessing self-reported mild, moderate, and strenuous physical activity (Godin), sedentary behavior (IPAQ), and bodyweight. Participants reported these variables for two separate time points: prior to the closure of campus due to the pandemic in March of 2020 and again at the time of the survey administration (May-June 2020). Participants also reported whether they did (n = 172) or did not (n = 232) regularly use physical activity monitoring devices. RESULTS: Two group (monitors, no monitors) by two time point (pre-, post-campus closure) ANOVAs revealed significant (p < 0.001) main effects of time for sitting and bodyweight but not for any measure of physical activity (p ≥ 0.15). On average, participants increased sitting by 67.8 ± 156.6 min/day and gained 1.4 ± 7.6 lbs. from pre- to post-campus closure. There were also significant (p ≤ 0.02) main effects of group as participants who used monitors reported 58% greater strenuous physical activity, 11% lower mild physical activity and 10% less sitting than those that did not use monitors. However, there were no significant (p ≥ 0.15) group by time interactions for any variable. CONCLUSIONS: While physical activity was not affected, participants reported significant increases in sedentary behavior and bodyweight during the COVID-19 pandemic. The use of a physical activity monitor did not moderate these effects.

Outdoor Activity: Benefits and Risks to Recreational Runners during the COVID-19 Pandemic

Running has become one of the most popular recreational sports worldwide. It is an easily accessible form of exercise as there are minimal equipment and sport structure requirements. Aerodynamic simulation experiments showed a risk of droplet exposure between runners when two people run in a straight line at a close distance (slipstream). Thus, running activities require a safe physical distance of 10 meters to avoid droplet exposure, which can be a source of transmission of COVID-19 infection. However, running outdoors during the COVID-19 pandemic is still often done in pairs and even in groups without wearing a mask. Open window theory stated that changes in the immune system occur immediately after strenuous physical activity. Many immune system components showed adverse changes after prolonged strenuous activity lasting more than 90 minutes. These changes occurred in several parts of the body, such as the skin, upper respiratory tract, lungs, blood, and muscles. Most of these changes reflected physiological stress and immunosuppression. It is thought that an “open window” of the compromised immune system occurs in the 3–72-hour period after vigorous physical exercise, where viruses and bacteria can gain a foothold, increasing the risk of infection, particularly in the upper respiratory tract. Outdoor physical activity positively affects psychological, physiological, biochemical health parameters, and social relationships. However, this activity requires clear rules so that the obtained benefits can be more significant while simultaneously minimizing the risk of transmission of COVID-19 infection.

Suspending Syntax: Bodily Strain and Progressivity in Talk

People speak not only under relaxed conditions but also during strenuous activities, and grammatical resources can be used to achieve displays of strain. This study looks at the relationship between progressivity of talk and bodily strain, focusing on the practice of temporarily suspending syntax while the speaker is accomplishing a physically challenging task. Based on examples from two different physical activities, rock climbing and opera rehearsals, the paper argues that the practice of suspending syntax is a resource available across contexts to render prominence to the strained body and highlight ongoing movement or other bodily action. By placing the strain-based display of incapacity to talk at a moment when the emerging syntactic structure is incomplete, participants maintain rights to resume talk while also presenting themselves as possessing the physical capacity to do so. Suspending syntax is shown to be a minutely timed speakers’ technique that takes advantage of the emergent nature of syntax and that demonstrates how speakers organize language in relation to the sensing and moving body.

Is e-sport a part of sports?

The purpose of this study is to describe the e-sports view of an athlete, the athlete in question is someone who is engaged in sports involving physical activity and movement with national scale achievements. The method in this research is observational with a quantitative descriptive design. The sample in this study amounted to 158 National athletes of Riau Province. The sampling technique represents all sports in Riau Province which are selected based on being in the appropriate situation, time, and place, with the purposive sampling technique. In this study, using a questionnaire instrument with a Likert scale, there were four category assessments, namely strongly agree, agree, disagree, strongly disagree. The data analysis used is a survey method carried out with a questionnaire and the scores obtained and an analysis of the e-sport category using the SPSS 25 application. The results reveal that sportsmen view e-sport as a sport even though there is no strenuous physical activity but there is light physical activity in it. especially in motor movement. The percentage acquisition of 14.6% is good. Then in the sufficient category, the percentage is 25.9%. While the moderate category of the presentation was 30.4%. For the category less the percentage is 20.9%. For the last category is bad 8.2%. The results reveal that sportsmen agree that e-sport is a sport. The results of the study are expected to be able to solve perceptions about e-sport in which there is no physical activity in it, which is a sport.

Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia.

Primary adrenal insufficiency (PAI) is characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. Addison's disease (AD) and congenital adrenal hyperplasia (CAH) are the most frequent disorders in adults and children, respectively. Despite the diagnostic advances and the availability of glucocorticoid and mineralocorticoid replacements, adrenal crisis (AC) is still a potentially lethal condition contributing to the increased mortality, not only during the first year of life, but also throughout life. Failure in increasing glucocorticoid doses during acute stress, when greater amounts of glucocorticoids are required, can lead to AC and an increase morbimortality rate of PAI. Considering a mortality rate of 0.5 per 100 patient years, up to 1,500 deaths from AC are expected in Brazil in the coming decade, which represents an alarming situation. The major clinical features are hypotension and volume depletion. Nonspecific symptoms such as fatigue, lack of energy, anorexia, nausea, vomiting, and abdominal pain are common. The main precipitating factors are gastrointestinal diseases, other infectious disease, stressful events (e.g., major pain, surgery, strenuous physical activity, heat, and pregnancy), and withdrawal of glucocorticoid therapy. Suspected AC requires immediate therapeutic action with intravenous (iv) hydrocortisone, fluid infusion, monitoring support, and antibiotics if necessary. AC is best prevented through patient education, precocious identification and by adjusting the glucocorticoid dosage in stressor situations. The emergency card, warning about acute glucocorticoid replacement, has high value in reducing the morbidity and mortality of AC.

Modulation of the Primary Auditory Thalamus When Recognizing Speech with Background Noise.

Recognizing speech in background noise is a strenuous daily activity, yet most humans can master it. An explanation of how the human brain deals with such sensory uncertainty during speech recognition is to-date missing. Previous work has shown that recognition of speech without background noise involves modulation of the auditory thalamus (medial geniculate body; MGB): there are higher responses in left MGB for speech recognition tasks that require tracking of fast-varying stimulus properties in contrast to relatively constant stimulus properties (e.g., speaker identity tasks) despite the same stimulus input. Here, we tested the hypotheses that (1) this task-dependent modulation for speech recognition increases in parallel with the sensory uncertainty in the speech signal, i.e., the amount of background noise; and that (2) this increase is present in the ventral MGB, which corresponds to the primary sensory part of the auditory thalamus. In accordance with our hypothesis, we show, by using ultra-high-resolution functional magnetic resonance imaging (fMRI) in male and female human participants, that the task-dependent modulation of the left ventral MGB (vMGB) for speech is particularly strong when recognizing speech in noisy listening conditions in contrast to situations where the speech signal is clear. The results imply that speech in noise recognition is supported by modifications at the level of the subcortical sensory pathway providing driving input to the auditory cortex.SIGNIFICANCE STATEMENT Speech recognition in noisy environments is a challenging everyday task. One reason why humans can master this task is the recruitment of additional cognitive resources as reflected in recruitment of non-language cerebral cortex areas. Here, we show that also modulation in the primary sensory pathway is specifically involved in speech in noise recognition. We found that the left primary sensory thalamus (ventral medial geniculate body; vMGB) is more involved when recognizing speech signals as opposed to a control task (speaker identity recognition) when heard in background noise versus when the noise was absent. This finding implies that the brain optimizes sensory processing in subcortical sensory pathway structures in a task-specific manner to deal with speech recognition in noisy environments.

Effects of Kegels Exercises and Fitness Exercises in Improving the Stress, Urge or Mixed Urinary Incontinence (U.I.) Among the Elderly Seniors Using an Adult Urinary Diaper Pad Method

Urinary incontinence (U.I.) is a medical condition in which there an inability to control the urine during rest or even in some strenuous activities. Aging, Overweight, anxiety, and stress were the predisposing factors in developing U.I. 28 healthy male volunteers between the age group of 65-75 were analyzed in this interventional study. A urinary diaper pad was used to assess the leakage during strenuous activities. According to the American college of sports medicine (ACSM) guidelines, the exercises were prescribed and executed. SPSS software version 18 has been used for the analysis of statistics obtained with a confidence interval of 95%. By implementing descriptive statistics Mean and standard deviations (S.D.) were noted. To get the effectiveness of the intervention, paired t-test was done, and a p-value with &lt;0.05 was set as a level of significance for all the tests conducted. Positive changes were observed in the reduction of urinary leakage among the participants. The present study reports about finding the effects of Kegels exercise and fitness exercises among the elderly seniors with Urinary Incontinence, designed by the guidelines provided by ACSM health-related fitness components.

Lifestyle Factors and Parkinson's Disease Risk in a Rural New England Case-Control Study.

Introduction Parkinson's disease (PD) is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results Suffering from “head trauma or a concussion” prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in “strenuous athletic activities.” We observed a 2.7-fold increased risk of PD associated with activities involving lead (adjusted p=0.038). Conclusion Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.

An Ensemble Model With Genetic Algorithm for Classification of Coronary Artery Disease

Coronary artery disease (CAD) is the most common form of heart disease and has become the primary reason for death. A correct and on-time diagnosis of CAD is very important. Diagnosis of CAD being a strenuous activity, scientists have planned different intelligent diagnostic frameworks for improved CAD diagnosis. Still, low CAD classification accuracy is an issue in these frameworks. In this paper, the authors propose a feature selection technique (FST) that utilizes a genetic algorithm (GA) with J48 classifier as the objective function to choose adequate features for better CAD classification accuracy. After feature removal, classification frameworks are used (i.e., artificial neural network [ANN]) like multilayer perceptron network (MLP), radial basis function network (RBFN), ANN-based ensemble model (ANN-EM), and deep neural network (DNN). Finally, this research proposes an integrated model of GA and ANN-EM for classification of CAD.

Exercise and genes linked to ALS

Human Genomics Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease with a genetic and environmental interaction. Lou Gehrig was a renowned professional American baseball player whose career was cut short by ALS, which has now also become known as Lou Gehrig's disease. Using Mendelian randomization (MR), which can help to identify genetic factors linked to phenotype, Julian et al. looked for genetic differences between individuals within the UK Biobank correlated with their activity level, including strenuous activity. From this, they identified genetic variants associated with ALS risk in individuals who regularly performed strenuous exercise. Of the validated ALS risk genes, 52% showed differential gene expression during exercise in individuals with such variants. Strenuous exercise is a highly heterogenous environmental factor, and more study is needed to determine how it becomes a risk factor for ALS. EBioMedicine 68 , 103397 (2021).

GAMBARAN KUALITAS TIDUR DAN FUNGSI KOGNITIF PADA PASIEN PPOK DI BBKPM MAKASSAR

Poor sleep quality in patients with Chronic Obstructive Pulmonary Disease is caused by shortness of breath, coughing and excessive secretion production. Someone who has good sleep quality will affect his cognitive function, where sleep stage is associated with cerebral blood flow. Increased oxygen consumption can help store memory and learning related to cognitive function. Disorders of cognitive function will affect someone's productivity and even loss of independence. The incidence of COPD increases every year. By BBKPM 2015 that there were 130 patients, 142 in 2016 and 182 in 2017. This study aimed to describe the quality of sleep and cognitive function in COPD patients.This was descriptive study in that number of sample was 52 from 182 populations diagnosed with COPD at BBKPM Makassar. Data collection applied PSQI questionnaires to measure sleep quality and MMSE questionnaire to measure cognitive function.The results revealed that from 52 respondents, 35 (67.3%) performed poor sleep quality while 17 (32.7%) had good sleep quality with average score on PSQI 6.92. In addition, from 52 respondents, 29 (55.8%) had impaired cognitive function while 23 (44.2%) had normal cognitive function with average score on MMSE 22.77.It concluded that patients with COPD experienced poor sleep quality and cognitive impairment. It is encouraged to COPD patients to reduce strenuous activities in order to avoid shortness of breath.

Quality Of Life Of Breast Cancer Survivors In Surabaya Breast Cancer Community

Background: Cancer is a deadly disease for anyone. One type of cancer is breast cancer. This type of cancer has a big psychological impact on sufferers because of the risk of breast removal surgery for sufferers so that cancer can destroy their future and changing quality of life. Decreased quality of life in women with breast cancer causes them to be unable to fulfill their roles, duties and also mantaining health status. Therefore, the purposes of this study are to identified quality of life women with breast cancer. &#x0D; Methods: The method of this study used descriptive analysis, the study was conducted in the breast cancer community in Surabaya, East Java. A total of 30 people became respondents to this study and filled in 30 questions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C-30 (EORTC QLQ C30). &#x0D; Results: The general health of the patients was an 664.25, which illustrates that the quality of life for cancer patients is in moderate condition. This is because in this study the last week symptoms such as shortness of breath, weakness, pain, difficulty sleeping, loss of appetite, nausea, vomiting, difficulty defecating, diarrhea, fatigue, difficulty concentrating, tension, difficulty walking close, lying in a chair / mattress is reduced or not. They still find it difficult to do strenuous activities, walk long distances, feel worried, have difficulty remembering and exper.ience financial difficulties. However, their lives are not disrupted due to physicality or therapy&#x0D; Conclusion: The general health of breast cancer patients in the Surabaya breast cancer community is an 664.25, which describes the quality of life of cancer patients in moderate condition . It is expected that the hospital can socialize about the group of breast cancer to patients so that patients can share experience, obtain various health-related information, and will make patients feel they have many friends with cancer fighters so that it will further improve the quality of life

Role of Symptom Burden in Disability Leave Among Patients with Myeloproliferative Neoplasms (MPNs): Findings from the Living with MPN Patient Survey

Background: Patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), experience a high symptom burden that compromises daily functioning and quality of life.Objective: To describe the prevalence and nature of medical disability leave (MDL) among patients with MPNs, and its relationship with MPN symptoms.Methods: An online survey of adult patients (aged 18-70 years) with MF, PV, or ET in the United States was conducted between April and November of 2016. Data collected included patient demographics, MPN diagnosis, MDL due to MPNs since diagnosis (short-term or long-term, date of leave and return), history of thrombotic events, MPN-related symptoms (using the MPN Symptom Assessment Form [MPN-SAF]), and physical, mental, and social functional status in the prior 7 days. MPN total symptom score (TSS) was calculated as the sum of the scores for the 10 symptoms included in the MPN-SAF. Symptoms and functional status were compared between patients who took MDL and patients with no employment change using the t-test and chi-square test, respectively.Results: Among the total of 904 patients that participated in the survey, 592 patients were employed at the time of MPN diagnosis; 147 (24.8%) subsequently took MDL because of their MPN (MF, 66/174 [37.9%]; PV, 55/248 [22.2%]; ET, 26/170 [15.3%]; Table 1), 293 (49.5%) reported no change in employment because of their MPN, and the remaining152 patients had other employment change (e.g., early retirement, hour reduction). Among patients who took MDL, the mean age at diagnosis was 46 years, 66% were female, the mean duration of disease was 6.6 years, and 31% had a history of thrombotic event (TE). Among patients with no employment change, the mean age at diagnosis was 48 years, 71% were female, the mean duration of disease was 5.9 years, and 15.4% had a history of TEs. The mean time from MPN diagnosis to the first MDL was 2.3 years. Overall, 29.9% of patients took ≥2 MDLs, 48.3% took long-term leave, and by the time of the survey 62.6% did not return to work after their latest MDL. Among those who returned to work, the mean length of leave was 4.3 months; 46.3% of those who took MDL received social security benefits. A significantly higher symptom burden was reported among those who had gone on MDL compared with those with no employment change (mean MPN-TSS: 42.9 vs 20.1; P <0.001; Table 2). Fatigue or tiredness, bone pain, and day or night sweats were the most severe symptoms among patients who took MDL. A higher proportion of patients who took MDL vs patients with no employment change had functional impairments, such as difficulty with strenuous physical activities (91.2% vs 64.8%), remembering things (90.5% vs 60.8%), and sleeping (84.4% vs 58.7%; all P <0.001).Conclusions: Approximately one quarter of employed patients took MDL because of their MPN, nearly one half of whom took long-term leave. Patients who took MDL had significantly higher symptom burden vs those with no employment change. Most patients who went on MDL did not return to the workforce. Effectively managing MPN diseases and associated symptoms may reduce disability leave among those patients. [Display omitted] DisclosuresYu:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Mesa:Galena: Consultancy; Gilead: Research Funding; Incyte Corporation: Research Funding; Novartis: Consultancy; Ariad: Consultancy; Celgene: Research Funding; Promedior: Research Funding; CTI: Research Funding.

Safety and Efficacy of Crizotinib in ALK-Positive Lymphomas: A Phase 1b Open-Label Study

IntroductionCrizotinib, an inhibitor of ALK, MET and ROS1, is approved for patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMT).MethodsIn this open-label, ongoing, multicenter, single-arm phase 1b study (PROFILE 1013 [NCT01121588]), male or female patients, aged ≥15 years, with ECOG performance status 0−3,with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg BID. Primary endpoints were safety and objective responses, based on RECIST v1.1 or NCI International Response Criteria.ResultsForty-four patients were enrolled (lymphoma=18, IMT=9, other tumors=17). In the lymphoma group, 17/18 of patients were evaluable for response. Objective response rate was 52.9% (95% CI 27.8-77.0) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 66.7% (95% CI 29.9-92.5) for IMT, with 1 CR and 5 PRs; and 11.8% (95% CI 1.5-36.4) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively.Median treatment duration was close to 3 years for lymphoma patients (150.7 weeks [range 0.1-249.3]) and IMT patients (142.9 weeks [range 21.1-160.0]) and was 1 month for patients with other tumors. Treatment with any other anti-cancer treatment was not allowed.In lymphoma patients, median PFS has not been reached due to a small number of events (33.3%) (Figure 1). The estimated probability of lymphoma patients being progression free at 2 years was 63.0% (95% CI: 35.3, 81.4). Median OS was also not reached as OS data were immature, with 72.2% of patients with lymphoma still alive at the cutoff (Figure 2). Only 1 patient received bone marrow transplant during crizotinib treatment and was censored for anti-tumor activity.In IMT patients, median PFS was also not reached due to a small number of events (33.3%)(Figure 1). The estimated probability of IMT patients being progression free at 2 years was 66.7% (95% CI: 28.2, 87.8). In addition, median OS was not reached as 66.7% of patients with IMT were alive at data cutoff (Figure 2).In the other tumors group median PFS was 1.3 months (95% CI: 1.1, 3.9) (Figure 1) with a high number of events (88.2%), PFS at 2 years was 6.3% (95% CI: 0.4, 24.7) and median OS was 8.3 months (95% CI: 2.2, 16.9) (Figure 2).Treatment-related adverse events (TRAEs) occurred in a total of 39 (88.6%) patients. Mild to moderate diarrhea and vision disorder were the most common TRAEs reported (45.5%), most of which were grade 1. Overall, 9 patients (20.5%) experienced a serious adverse event (SAE) considered to be related to crizotinib treatment. The most common SAE considered as possibly treatment-related was grade 4 blood creatine phosphokinase increase reported in 3 patients (6.8%), all in clinical response and concurrent with strenuous physical activity. Grade 5 AEs considered by the investigator as treatment-related occurred in 2 patients: cerebral infarction in a patient with unknown primary tumor and multiple brain metastasis, concurrent with disease progression, and interstitial lung disease in a patient with nasopharyngeal carcinoma. Subsequent review by an independent radiology committee, consisting of a pulmonologist, radiologist and oncologist, indicated that this event was aspiration pneumonia, non-drug-related.ConclusionsThese findings indicate a strong and durable activity of crizotinib in ALK-positive lymphomas and IMTs. Treatment duration was much longer than usual treatment in NSCLC patients and the safety profile was consistent with the known safety profile of crizotinib, even with long-term treatment. [Display omitted] DisclosuresGambacorti-Passerini:BMS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Braiteh:Merck: Honoraria, Other: Travels, Speakers Bureau; Lexicon: Honoraria; Insys: Honoraria, Other: Travels, Speakers Bureau; Ipsen: Honoraria, Other: Travels, Speakers Bureau; Incyte: Honoraria, Other: Travels, Speakers Bureau; Heron Therapeutics: Honoraria, Other: Travels; Halozyme Therapeutics: Other: Travels; Eli Lilly: Honoraria, Other: Travels, Speakers Bureau; Clovis: Honoraria, Speakers Bureau; Celgene: Other: Travels, Speakers Bureau; Bristol Myers Squibb: Other: Travels, Speakers Bureau; Boehringer Ingelheim: Honoraria, Other: Travels, Speakers Bureau; Biotheranostics: Honoraria, Speakers Bureau; Bayer: Honoraria, Other: Travels; Astra Zeneca/Medimmune: Honoraria, Other: Travels, Speakers Bureau; Amgen: Honoraria, Other: Travels, Speakers Bureau; Merrimack: Honoraria, Other: Travels, Speakers Bureau; Pfizer: Honoraria, Other: Travels, Speakers Bureau; Roche/Genentech: Honoraria, Other: Travels, Speakers Bureau. Ahn:Boehringer Ingelheim: Honoraria; Menarini: Honoraria; Roche: Honoraria; Janssen: Honoraria; Eisai: Honoraria; BMS: Honoraria. Taylor:Eisai Inc.: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Trillium Therapeutics: Consultancy, Honoraria; Blue Print Medicines: Consultancy, Honoraria. Van Tine:Pfizer: Research Funding; Novartis: Consultancy, Speakers Bureau; Merch: Research Funding; Lilly: Consultancy, Speakers Bureau; J&J: Consultancy, Speakers Bureau; Caris: Consultancy, Speakers Bureau. Wu:Celgene International Sàrl: Research Funding. Paolini:Pfizer: Employment, Equity Ownership. Li:Pfizer: Employment.