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"Goldman, M"
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Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia
Imatinib mesylate is considered standard of care for first-line treatment of chronic phase chronic myeloid leukemia (CML-CP). In the phase III, randomized, open-label International Randomized Study of Interferon vs STI571 (IRIS) trial, previously untreated CML-CP patients were randomized to imatinib (
n
=553) or interferon-α (IFN) plus cytarabine (
n
=553). This 6-year update focuses on patients randomized to receive imatinib as first-line therapy for newly diagnosed CML-CP. During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC). The toxicity profile was unchanged. The cumulative best complete cytogenetic response (CCyR) rate was 82%; 63% of all patients randomized to receive imatinib and still on study treatment showed CCyR at last assessment. The estimated event-free survival at 6 years was 83%, and the estimated rate of freedom from progression to AP and BC was 93%. The estimated overall survival was 88%––or 95% when only CML-related deaths were considered. This 6-year update of IRIS underscores the efficacy and safety of imatinib as first-line therapy for patients with CML.
Journal Article
أهم خمسة أسئلة لبيتر دراكر : حكمة دائمة للقادة الشباب
كثيرا ما سأل بيتر إف. دراكر الأشخاص الذين عمل معهم سؤالا بسيطا : كيف تريدون أن يتذكركم الناس ؟. وفي معهد فرانسيس هيسبين للقيادة، وافقنا بالإجماع على مدى أهمية أن نلعب دورا في إلهام الجيل التالي من القادة. وفي عام 2009، اشترك معهد هيسبين مع جامعة بيتسبرج في إطلاق مشروع أكاديمية هيسبين العالمية للقيادة الطلابية والمشاركة المدنية، الذي استقطب 300 طالب موهوب من جميع القارات وعرض عليهم أعمال بيتر دراكر وفرانسيس هيسبين. إن الجيل الأصغر سنا في يومنا هذا-المعروف بجيل الألفية أو الجيل واي، المولود في الفترة ما بين عامي 1980 و 2000-ليس هو الجيل الأكبر بعد، ولكنه أكثر الأجيال تعلما وتنوعا ؛ فقد ضخم حجم التكنولوجيا وسهولة السفر حول العالم من أحلامهم بالعديد من الطرق. وجعلتهم حركة شبكات التواصل الاجتماعي والإعلام الرقمي، بدءا من القنوات المشفرة التقليدية ووصولا إلى مواقع ألفيس بوك وتويتر متواصلين مع بقية العالم بحيث يمكنهم ارتداء الماركات العالمية وكذلك التفاعل مع القضايا حول العالم بطرق استباقية جديدة. كما طوروا شبكات أصدقاء لم تتضمن الجيران أو رفقاءهم في صفوف الرياضة فقط بل تضمنت أصدقاء من أماكن نائية من العالم. ربما لم يلتقوا بهؤلاء الأصدقاء من قبل وجها لوجه، ولكن التواصل فيما بينهم كان له تأثير كبير على حيواتهم، كما نمى لديهم شعورا بالتعاطف العالمي، ولهذا أنا غالبا ما أشير إلى جيل الألفية بأنه الجيل العالمي الأول.
BOOK
Remote smartphone monitoring of Parkinson’s disease and individual response to therapy
Remote health assessments that gather real-world data (RWD) outside clinic settings require a clear understanding of appropriate methods for data collection, quality assessment, analysis and interpretation. Here we examine the performance and limitations of smartphones in collecting RWD in the remote mPower observational study of Parkinson’s disease (PD). Within the first 6 months of study commencement, 960 participants had enrolled and performed at least five self-administered active PD symptom assessments (speeded tapping, gait/balance, phonation or memory). Task performance, especially speeded tapping, was predictive of self-reported PD status (area under the receiver operating characteristic curve (AUC) = 0.8) and correlated with in-clinic evaluation of disease severity (
r
= 0.71;
P
< 1.8 × 10
−6
) when compared with motor Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Although remote assessment requires careful consideration for accurate interpretation of RWD, our results support the use of smartphones and wearables in objective and personalized disease assessments.
Smartphone sensors that monitor disease symptoms enable remote assessment of Parkinson’s patients.
Journal Article
Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease
Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD-rs6812193 near SCARB2 (p = 7.6 × 10(-10), OR = 0.84) and rs11868035 near SREBF1/RAI1 (p = 5.6 × 10(-8), OR = 0.85)-both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%-7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered.
Journal Article
A Phase 2 Trial of Ponatinib in Philadelphia Chromosome–Positive Leukemias
Several tyrosine kinase inhibitors have activity in Ph-positive chronic and acute leukemia, but resistant disease and unacceptable side effects may limit efficacy. Ponatinib showed a high level of activity in a phase 2 study of tyrosine kinase inhibitor–resistant disease but was associated with arterial thrombosis.
Patients with newly diagnosed chronic myeloid leukemia (CML) frequently receive imatinib. Although initial response rates are high, imatinib fails in up to 40% of patients because of disease resistance, frequently because of BCR-ABL kinase domain mutations or unacceptable side effects.
1
,
2
Patients who discontinue imatinib may have a response to second-generation tyrosine kinase inhibitors. However, 37 to 52% of patients do not have a response,
3
–
8
and 23 to 26% of patients have an initial major cytogenetic response that is lost by 2 years.
3
,
9
The prognosis for these patients is very poor. With the exception of the small number . . .
Journal Article
Benralizumab for the Prevention of COPD Exacerbations
In patients with moderate to very severe COPD and a blood eosinophil count of 220 cells per cubic millimeter or greater, treatment with benralizumab, an anti–interleukin-5 receptor antibody (administered at doses similar to or higher than those used for severe asthma) did not change the rate of COPD exacerbations.
Journal Article
Gradient boosting for Parkinson’s disease diagnosis from voice recordings
Background
Parkinson’s Disease (PD) is a clinically diagnosed neurodegenerative disorder that affects both motor and non-motor neural circuits. Speech deterioration (hypokinetic dysarthria) is a common symptom, which often presents early in the disease course. Machine learning can help movement disorders specialists improve their diagnostic accuracy using non-invasive and inexpensive voice recordings.
Method
We used “Parkinson Dataset with Replicated Acoustic Features Data Set” from the UCI-Machine Learning repository. The dataset included 44 speech-test based acoustic features from patients with PD and controls. We analyzed the data using various machine learning algorithms including Light and Extreme Gradient Boosting, Random Forest, Support Vector Machines, K-nearest neighborhood, Least Absolute Shrinkage and Selection Operator Regression, as well as logistic regression. We also implemented a variable importance analysis to identify important variables classifying patients with PD.
Results
The cohort included a total of 80 subjects: 40 patients with PD (55% men) and 40 controls (67.5% men). Disease duration was 5 years or less for all subjects, with a mean Unified Parkinson’s Disease Rating Scale (UPDRS) score of 19.6 (SD 8.1), and none were taking PD medication. The mean age for PD subjects and controls was 69.6 (SD 7.8) and 66.4 (SD 8.4), respectively. Our best-performing model used Light Gradient Boosting to provide an AUC of 0.951 with 95% confidence interval 0.946–0.955 in 4-fold cross validation using only seven acoustic features.
Conclusions
Machine learning can accurately detect Parkinson’s disease using an inexpensive and non-invasive voice recording. Light Gradient Boosting outperformed other machine learning algorithms. Such approaches could be used to inexpensively screen large patient populations for Parkinson’s disease.
Journal Article
Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome
Benralizumab, an interleukin-5 receptor blocker, significantly reduced absolute eosinophil counts and relieved symptoms in a small group of patients with hypereosinophilic syndrome. Adverse events were similar in the benralizumab group and the placebo group.
Journal Article
Plant-Based Diets for Cardiovascular Safety and Performance in Endurance Sports
Studies suggest that endurance athletes are at higher-than-average risk for atherosclerosis and myocardial damage. The ability of plant-based regimens to reduce risk and affect performance was reviewed. The effect of plant-based diets on cardiovascular risk factors, particularly plasma lipid concentrations, body weight, and blood pressure, and, as part of a healthful lifestyle, reversing existing atherosclerotic lesions, may provide a substantial measure of cardiovascular protection. In addition, plant-based diets may offer performance advantages. They have consistently been shown to reduce body fat, leading to a leaner body composition. Because plants are typically high in carbohydrate, they foster effective glycogen storage. By reducing blood viscosity and improving arterial flexibility and endothelial function, they may be expected to improve vascular flow and tissue oxygenation. Because many vegetables, fruits, and other plant-based foods are rich in antioxidants, they help reduce oxidative stress. Diets emphasizing plant foods have also been shown to reduce indicators of inflammation. These features of plant-based diets may present safety and performance advantages for endurance athletes. The purpose of this review was to explore the role of nutrition in providing cardioprotection, with a focus on plant-based diets previously shown to provide cardiac benefits.
Journal Article