bluuebunny/crossref_metadata_2025 huggingface dataset:
Germline Genetic Predisposition to Hematologic Malignancy
Authors: Furutani Elissa , Shimamura Akiko
Published: February 2017

Development of hematologic malignancies is driven by mutations that may be somatic or germline. Availability of next-generation DNA sequencing technologies has facilitated the development of individualized diagnostic evaluations and tailored treatment strategies. Until now, such personalized medical approaches have largely centered on prognostic stratification and treatment strategies informed by acquired somatic mutations. The role of germline mutations in children and adults with hematologic malignancies was previously underappreciated. Diagnosis of an inherited predisposition to hematologic malignancy informs choice of therapy, risk of treatment-related complications, donor selection for hematopoietic stem cell transplantation, evaluation of comorbidities, and surveillance strategies to improve clinical outcomes. The recognition that patients with inherited hematologic malignancy syndromes may present without classic clinical stigmata or suspicious family history has led to increased reliance on genetic testing, which, in turn, has raised new diagnostic challenges. Genomic testing is a rapidly evolving field with an increasing number of choices for testing for the practicing clinician to navigate. This review will discuss general approaches to diagnosis and management of patients with germline predisposition to hematology malignancies and will consider applications and limitations of genomic testing in clinical practice.
Genomics of Hairy Cell Leukemia
Authors: Tiacci Enrico , Pettirossi Valentina , Schiavoni Gianluca , Falini Brunangelo
Published: February 2017

Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. Conversely, BRAF-V600E is absent in other B-cell neoplasms, including mimickers of HCL that require different treatments (eg, HCL-variant and splenic marginal zone lymphoma). Thus, testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, even noninvasively in routine blood samples. BRAF-V600E also represents a new therapeutic target. Patients’ leukemic cells exposed ex vivo to BRAF inhibitors are spoiled of their HCL identity and then undergo apoptosis. In clinical trials of patients with HCL who have experienced multiple relapses after purine analogs or who are refractory to purine analogs, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, including complete remission rates of 35% to 42%, without myelotoxicity. To further improve on these results, it will be important to clarify the mechanisms of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combinations of a BRAF inhibitor with other targeted agents (eg, a MEK inhibitor and/or an anti-CD20 monoclonal antibody).
Genomics of Acute Myeloid Leukemia Diagnosis and Pathways
Authors: Bullinger Lars , Döhner Konstanze , Döhner Hartmut
Published: February 2017

In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such mutations may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. In contrast, mutations involving NPM1 or signaling molecules (eg, FLT3, RAS) typically are secondary events that occur later during leukemogenesis. Genetic data are now being used to inform disease classification, risk stratification, and clinical care of patients. Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current update of the WHO classification of myeloid neoplasms and AML, and mutations in three genes— RUNX1, ASXL1, and TP53—have been added in the risk stratification of the 2017 European LeukemiaNet recommendations for AML. Integrated evaluation of baseline genetics and assessment of minimal residual disease are expected to further improve risk stratification and selection of postremission therapy. Finally, the identification of disease alleles will guide the development and use of novel molecularly targeted therapies.
Wilms Tumor Treatment Outcomes: Perspectives From a Low-Income Setting
Authors: Njuguna Festus , Martijn Hugo A. , Kuremu Robert Tenge , Saula Peter , Kirtika Patel , Olbara Gilbert , Langat Sandra , Martin Steve , Skiles Jodi , Vik Terry , Kaspers Gertjan J.L. , Mostert Saskia
Published: February 2017

Purpose

Wilms tumor is the commonest renal malignancy in childhood. Survival in high-income countries is approximately 90%, whereas in low-income countries, it is less than 50%. This study assessed treatment outcomes of patients with Wilms tumor at a Kenyan academic hospital.

Patients and Methods

We conducted a retrospective medical record review of all children diagnosed with Wilms tumor between 2010 and 2012. Data on treatment outcomes and various sociodemographic and clinical characteristics were collected.

Results

Of the 39 patients with Wilms tumor, 41% had event-free survival, 31% abandoned treatment, 23% died, and 5% had progressive or relapsed disease. Most patients presented at an advanced stage: stage I (0%), II (7%), III (43%), IV (40%), or V (10%). The most likely treatment outcome in patients with low-stage (I to III) disease was event-free survival (67%), whereas in those with high-stage (IV to V) disease, it was death (40%). No deaths or instances of progressive or relapsed disease were recorded among patients with low-stage disease; their only reason for treatment failure was abandonment of treatment. Stage of disease significantly affected treatment outcomes ( P = .014) and event-free survival estimates ( P < .001). Age at diagnosis, sex, duration of symptoms, distance to hospital, and health insurance status did not statistically significantly influence treatment outcomes or event-free survival estimates.

Conclusion

Survival of patients with Wilms tumor in Kenya is lower compared with that in high-income countries. Treatment abandonment is the most common cause of treatment failure. Stage of disease at diagnosis statistically significantly affects treatment outcomes and survival.
Acceptability of Human Papillomavirus Self-Sampling for Cervical Cancer Screening in an Indigenous Community in Guatemala
Authors: Gottschlich Anna , Rivera-Andrade Alvaro , Grajeda Edwin , Alvarez Christian , Mendoza Montano Carlos , Meza Rafael
Published: February 2017

Purpose

Cervical cancer rates in Latin America are higher than those in developed countries, likely because of the lower prevalence of screening. Specifically, less than 40% of women in Guatemala are regularly screened and even fewer women are screened in indigenous communities. Current screening strategies—Pap smears and visual inspection with acetic acid—might not be the most effective methods for controlling cancer in these settings. We thus investigated the potential of self-collection of cervical samples with testing for human papillomavirus (HPV) to help prevent cervical cancer in an indigenous community in Guatemala.

Patients and Methods

A community representative random sample of 202 indigenous women age 18 to 60 years residing in Santiago Atitlan, Guatemala, were surveyed to assess knowledge of and risk factors for HPV and cervical cancer. Women were then invited to self-collect a cervical sample using HerSwab collection kits to assess the prevalence of HPV and the acceptability of self-sampling.

Results

Of 202 women who completed the survey, 178 (89%) provided a self-sample. In all, 79% of these women found the test comfortable, 91% found the test easy to use, and 100% reported they were willing to perform the test periodically as a screening method. Thirty-one samples (17%) were positive for at least one of 13 high-risk HPV types, and eight (4.5%) were positive for HPV 16/18.

Conclusion

HPV testing by using self-collected samples was well accepted, suggesting that it is a plausible modality for cervical cancer screening in indigenous communities. Further studies are needed to assess rates of follow-up after a positive test and to determine whether these findings extend to other indigenous and nonindigenous communities in Guatemala and Latin America.
Applicability of the National Comprehensive Cancer Network/Multinational Association of Supportive Care in Cancer Guidelines for Prevention and Management of Chemotherapy-Induced Nausea and Vomiting in Southeast Asia: A Consensus Statement
Authors: Chan Alexandre , Abdullah Matin M. , Ishak Wan Zamaniah B. Wan , Ong-Cornel Annielyn B. , Villalon Antonio H. , Kanesvaran Ravindran
Published: February 2017

A meeting of regional experts was convened in Manila, Philippines, to develop a resource-stratified chemotherapy-induced nausea and vomiting (CINV) management guideline. In patients treated with highly emetogenic chemotherapy in general clinical settings, triple therapy with a serotonin (5-hydroxytryptamine-3 [5-HT3]) antagonist (preferably palonosetron), dexamethasone, and aprepitant is recommended for acute CINV prevention. In resource-restricted settings, triple therapy is still recommended, although a 5-HT3 antagonist other than palonosetron may be used. In both general and resource-restricted settings, dual therapy with dexamethasone (days 2 to 4) and aprepitant (days 2 to 3) is recommended to prevent delayed CINV. In patients treated with moderately emetogenic chemotherapy, dual therapy with a 5-HT3 antagonist, preferably palonosetron, and dexamethasone is recommended for acute CINV prevention in general settings; any 5-HT3 antagonist can be combined with dexamethasone in resource-restricted environments. In general settings, for the prevention of delayed CINV associated with moderately emetogenic chemotherapy, corticosteroid monotherapy on days 2 and 3 is recommended. If aprepitant is used on day 1, it should be continued on days 2 and 3. Prevention of delayed CINV with corticosteroids is preferred in resource-restricted settings. The expert panel also developed CINV management guidelines for anthracycline plus cyclophosphamide combination schedules, multiday cisplatin, and chemotherapy with low or minimal emetogenic potential, and its recommendations are detailed in this review. Overall, these regional guidelines provide definitive guidance for CINV management in general and resource-restricted settings. These consensus recommendations are anticipated to contribute to collaborative efforts to improve CINV management in Southeast Asia.
Multidisciplinary Gynecologic Oncology Clinic in Botswana: A Model for Multidisciplinary Oncology Care in Low- and Middle-Income Settings
Authors: Grover Surbhi , Chiyapo Sebathu Philip , Puri Priya , Narasimhamurthy Mohan , Gaolebale Babe Eunice , Tapela Neo , Ramogola-Masire Doreen , Kayembe Mukendi K.A. , Moloi Thabo , Gaolebale Ponatshego Andrew
Published: February 2017

Purpose

Cervical cancer is a major cause of mortality in low- and middle-income countries (LMICs) and the most common cancer diagnosed in women in Botswana. Most women present with locally advanced disease, requiring chemotherapy and radiation. Care co-ordination requires input from a multidisciplinary team (MDT) to deliver appropriate, timely treatment. However, there are limited published examples of MDT implementation in LMICs.

Methods

In May 2015, a weekly MDT clinic for gynecologic cancer care was initiated at Botswana’s national referral facility. The MDT clinic served as a forum for discussion and coordination of patients with gynecologic cancer and consisted of a gynecologist, pathologist, medical oncologist, radiation oncologist, palliative care specialist, and nurse coordinator.

Results

Between May 2015 and December 2015, 135 patients were seen in the MDT clinic. The mean age of the patients was 49 years. Most (60%) of the patients were HIV positive. The most common diagnosis was cervical cancer (60%), followed by high-grade cervical intraepithelial neoplastic lesions (12%) and vulvar cancer (11%). Only data up to September 2015 were assessed for treatment delays. It was found that only 38% of patients needed more than one visit for care coordination before treatment initiation. Among patients with cervical cancer, the median delay from date of biopsy to start of radiation treatment was 39 days (interquartile range, 34 to 57 days) for patients treated after MDT initiation, compared with 108 days (interquartile range, 71 to 147 days) for patients treated before MDT initiation ( P < .001).

Conclusion

Implementation of MDT clinics in LMICs is feasible and can help reduce delays in treatment initiation, as demonstrated by a gynecologic MDT clinic in Botswana. Streamlining care through MDT clinics can enhance care coordination and improve clinical outcomes. This model can apply to cancer care in other LMICs.
Comparison of Symptom Score and Bronchoscopy-Based Assessment With Conventional Computed Tomography–Based Assessment of Response to Chemotherapy in Lung Cancer
Authors: Yenge Lakshimikant Baburao , Behera Digambar , Garg Mandeep , Aggarwal Ashutosh Nath , Singh Navneet
Published: February 2017

Purpose

There is a paucity of literature on symptom score (SS) plus fiberoptic bronchoscopy (FOB) –based response evaluation (RE) to chemotherapy for lung cancer. This study aimed to compare the reliability of RE by SS, chest radiograph (CXR), and FOB with computed tomography (CT) –based assessment (Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria) for lung cancer chemotherapy.

Methods

This was a prospective observational study involving treatment-naïve patients with lung cancer planned for chemotherapy, with one or more lesions on FOB and CT. Patients underwent assessment twice by SS, CXR, FOB, and CT (at baseline and after chemotherapy). Six symptoms (dyspnea, cough, chest pain, hemoptysis, anorexia, and weight loss) were noted on visual analog scale. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from the first four and all six symptoms, respectively, as the mean of individual SS. Bronchoscopic findings were recorded as per European Respiratory Society classification for tracheobronchial stenosis. Responses were classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by each method. For FOB and SS, improvement or worsening by ≥ 20% was taken as PR or PD, respectively, whereas < 20% change was considered SD. Agreements were tested using Cohen’s κ statistic.

Results

All individual SS, RSB, and TSB scores, and the number and distribution of FOB lesions improved significantly after chemotherapy. Individually, CXR and SS had no or minimal agreement with FOB-based and CT-based responses. RECIST and WHO criteria had strong agreement overall (Cohen’s κ = 0.872) and perfect agreement for PD (Cohen’s κ = 1.000). Cohen’s κvalues for FOB-based assessment with RECIST and WHO were 0.324 and 0.349, respectively for overall RE, and 0.462 and 0.501 for differentiating responders (CR and PR) from nonresponders (SD and PD), respectively. Cohen’s κvalues for PD were 0.629 (FOB alone), 0.672 (FOB and RSB), 0.739 (FOB and TSB), and 0.764 (FOB and CXR).

Conclusion

CT-based assessment should remain the reference for objective RE of chemotherapy in lung cancer. A combination of FOB and CXR may be used as a surrogate to diagnose PD if CT is not feasible.
Beliefs and Determinants of Use of Traditional Complementary/Alternative Medicine in Pediatric Patients Who Undergo Treatment for Cancer in South America
Authors: Rocha Valeria , Ladas Elena J. , Lin Meiko , Cacciavillano Walter , Ginn Elizabeth , Kelly Kara M. , Chantada Guillermo , Castillo Luis
Published: February 2017

Purpose

The use of traditional complementary/alternative medicine (TCAM) among children with cancer has been well documented. South America has a rich history of traditional healers and medicinal resources; however, little is known about the use of TCAM among children with cancer. We sought to investigate patterns, beliefs, and determinants of TCAM use among South American children with cancer.

Methods

A cross-sectional survey was administered to 199 children treated for cancer at institutions located in Buenos Aires, Argentina, and Montevideo, Uruguay. Participants were queried about the type of TCAM and strength of beliefs associated with its use. Logistic regression analysis was used to estimate the odds ratios with 95% CIs.

Results

We found that the use of TCAM was common in both Argentina (47%) and Uruguay (76%). Variations in the forms of TCAM used were observed between the countries; however, both countries used TCAM primarily for supportive care. Mother’s education, wealth index, and TCAM belief system were significant predictors of TCAM.

Conclusion

To our knowledge, this study is the first to report on the use of TCAM in pediatric oncology in South America. The study identifies several predictors of TCAM use, which may serve as target variables for educational and research initiatives. The finding that most families use TCAM for supportive care suggests that future efforts could evaluate the role of TCAM to enhance existing supportive care regimens, particularly in settings where access to conventional medications are limited.
Chemotherapy in Nonmetastatic Osteosarcoma: Recent Advances and Implications for Developing Countries
Authors: Rastogi Sameer , Aggarwal Aditi , Tiwari Akash , Sharma Vinod
Published: February 2017

Purpose

Osteosarcoma (OS) is a relatively chemosensitive primary bone tumor, with the peak age of onset occurring in late childhood and early adolescence. The treatment paradigm of nonmetastatic OS has typically been multimodality therapy, including neoadjuvant and adjuvant chemotherapy with definitive surgery. Over the years, various permutations and combinations of chemotherapeutic agents have been used. However, the majority of recent trials have still used high-dose methotrexate as the backbone, with cisplatin and doxorubicin (MAP). In the last decade, various strategies targeted to improving outcomes in OS have included the addition of a fourth drug to the three-drug MAP regimen, changing therapy according to histopathologic response and the addition of immunotherapies. Through this review, we sought to underscore a few pertinent issues related to chemotherapy in nonmetastatic OS, with special reference to challenges confronted in Indian settings.

Methods

We reviewed the literature, focusing on studies comparing high-dose methotrexate and non–high-dose methotrexate–containing regimens. In addition, this review focuses on non–methotrexate-containing triple-drug therapy.

Results

Although a high-dose methotrexate regimen has become standard of care in developed countries, there are few data to suggest that it is superior to a non–high-dose methotrexate regimen.

Conclusion

Developing countries with lack of infrastructure and logistics for high-dose methotrexate might resort to non–high-dose methotrexate–containing regimens with a simultaneous focus on early detection, decreasing abandonment, multidisciplinary clinics, improved surgery, and meticulous pathologic evaluations.
Knowledge and Attitudes About Breast Cancer in Limpopo, South Africa
Authors: Trupe Lydia A. , Rositch Anne , Dickerson Lindsay , Lucas Su , Harvey Susan C.
Published: February 2017

Purpose

Breast cancer survival is unacceptably low in many low-resource settings, including rural South Africa, where access to screening and treatment services is limited. To describe the context for implementing an early detection program, we assessed knowledge and attitudes toward breast cancer risk, early detection, and treatment.

Methods

We conducted a cross-sectional survey among 243 women presenting to Hlokomela Clinic in Hoedspruit, South Africa, during April and May 2016. We used quantitative and qualitative analyses to determine levels of knowledge of risk factors, symptoms, and treatment of breast cancer, as well as experience with and attitudes toward detection and treatment methods.

Results

Thirty-one percent of women correctly identified at least six of 12 risk factors for breast cancer, and 53.1% identified breast lumps as an important symptom. Although > 97% of women stated that self–breast examination and early detection were highly important and that they would seek care for changes in their breasts, only 33.3% of women reported performing self–breast examination, and only 24.3% reported receiving a clinical breast examination. Age and education were not associated with knowledge, and level of knowledge did not predict care-seeking behaviors or attitudes.

Conclusion

Although women demonstrated moderate levels of knowledge of breast cancer symptoms and risk factors and the importance of early detection, few women reported seeking services. These data demonstrate sufficient levels of knowledge and positive attitudes toward care seeking and suggest both a need and readiness for increased access to cost-effective services to facilitate early diagnosis and improved outcomes.
Phase II Trial on Extending the Maintenance Flushing Interval of Implanted Ports
Authors: Diaz Jorge A. , Rai Shesh N. , Wu Xiaoyoung , Chao Ju-Hsien , Dias Ajoy L. , Kloecker Goetz H.
Published: February 2017

Purpose:

Retrospective studies suggest that it may be safe to extend the maintenance flushing interval of implanted ports from once every month, as recommended by the manufacturer, to once every 3 months, but no prospective cohort studies have been done specifically assessing the safety and feasibility of this intervention.

Methods:

This was a phase II study in oncologic patients who retained a functional port after completion of systemic chemotherapy. Patients enrolled in the study had their port flushed once every 3 months and were observed until completion of five scheduled flushes (one on enrollment and four additional flushes, one every 3 months) or development of any port-related complication, including infections, thrombosis, and occlusions. The primary end points were frequency of port-related complications and port failure requiring removal.

Results:

A total of 87 patients were enrolled in the study. The median follow-up time was 308 days, accounting for a total of 24,202 catheter-days. There were 10 port-related complications (11.49%; 95% CI, 4.85% to 18.14%). No infection or symptomatic thrombosis occurred. The mean time to port-related complication was 184 days. No patients developed port failure while on protocol, but on subsequent medical record review, four patients developed a complication that required port removal or port revision within 30 days of being removed from the trial (4.6%; 95% CI, 0.4% to 8.8%; 0.17/1,000 catheter-days).

Conclusion:

Extending the maintenance flushes of implanted ports in adult oncologic patients to once every 3 months is safe, effective, and likely to increase patient adherence and satisfaction while decreasing the associated cost.
Risk Factors and Patterns of Potentially Avoidable Readmission in Patients With Cancer
Authors: Donzé Jacques D. , Lipsitz Stuart , Schnipper Jeffrey L.
Published: February 2017

Purpose:

Patients with cancer are particularly at risk for readmission within 30-days after discharge. To identify the patients who might benefit from more-intensive discharge interventions, we identified the risk factors associated with 30-day potentially avoidable readmissions.

Methods and Materials:

We included all consecutive discharges from the oncology division of an academic tertiary medical center in Boston, Massachusetts, between July 1, 2009, and June 30, 2010. Potentially avoidable 30-day readmissions to the index hospital and two other hospitals within its network were identified. We performed a multivariable logistic regression in which the final model included variables found in bivariable testing to be significantly associated with the outcome.

Results:

Among the 2,916 patients discharged during the study period, 1,086 (37.3%) were readmitted within 30 days. Of these, 341 (31.4% of all readmissions, 11.7% of all discharges) were identified as potentially avoidable. In the multivariable analysis, the following patient factors were associated with a significantly higher risk of a potentially avoidable readmission: total number of medications at discharge, liver disease, last sodium level, and last hemoglobin level before discharge. In addition, potentially avoidable readmissions occurred significantly earlier than unavoidable readmissions (median, 10 v 13 days; P < .001).

Conclusion:

Almost 40% of patients with cancer had a 30-day readmission, and almost one third of these were deemed potentially avoidable, and several risk factors for this were identified. Interventions at discharge may be prioritized to patients with these risk factors.
Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer
Authors: Foote Jonathan R. , Lopez-Acevedo Micael , Buchanan Adam H. , Secord Angeles Alvarez , Lee Paula S. , Fountain Cynthia , Myers Evan R. , Cohn David E. , Reed Shelby D. , Havrilesky Laura J.
Published: February 2017

Purpose:

The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies.

Methods:

A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed.

Results:

No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs.

Conclusion:

MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.
Cancer Drugs: An International Comparison of Postlicensing Price Inflation
Authors: Savage Philip , Mahmoud Sarah , Patel Yogin , Kantarjian Hagop
Published: February 2017

Purpose:

The cost of cancer drugs forms a rising proportion of health care budgets worldwide. A number of studies have examined international comparisons of initial cost, but there is little work on postlicensing price increases. To examine this, we compared cancer drug prices at initial sale and subsequent price inflation in the United States and United Kingdom and also reviewed relevant price control mechanisms.

Methods:

The 10 top-selling cancer drugs were selected, and their prices at initial launch and in 2015 were compared. Standard nondiscounted prices were obtained from the relevant annual copies of the RED BOOK and the British National Formulary.

Results:

At initial marketing, prices were on average 42% higher in the United States than in the United Kingdom. After licensing in the United States, all 10 drugs had price rises averaging an overall annual 8.8% (range, 1.4% to 24.1%) increase. In comparison, in the United Kingdom, six drugs had unchanged prices, two had decreased prices, and two had modest price increases. The overall annual increase in the United Kingdom was 0.24%.

Conclusion:

Cancer drug prices are rising substantially, both at their initial marketing price and, in the United States, at postlicensing prices. In the United Kingdom, the Pharmaceutical Price Regulation Scheme, an agreement between the government and the pharmaceutical industry, controls health care costs while allowing a return on investment and funds for research. The increasing costs of cancer drugs are approaching the limits of sustainability, and a similar government-industry agreement may allow stability for both health care provision and the pharmaceutical industry in the United States.
Orthodox Jewish Thought Leaders’ Insights Regarding BRCA Mutations: A Descriptive Study
Authors: Bressler Toby , Popp Beth
Published: February 2017

Purpose:

To examine the factors that influence Orthodox Jewish (OJ) thought leaders’ perceptions of genetic counseling and testing for BRCA mutations. The specific aims of this study were to describe (1) OJ thought leaders’ views on genetic counseling and testing for BRCA mutation status and (2) insights into this high-risk faith-based minority group and their beliefs about counseling and testing for BRCA mutations.

Methods:

In-depth focus groups and demographic questionnaires were used in this descriptive, qualitative study, which was performed in the cancer center of a 750-bed community teaching hospital in Brooklyn, New York. Participants included 17 OJ thought leaders in a large metropolitan area in the northeastern United States.

Results:

Four themes emerged that describe the key components of the views of OJ thought leaders regarding genetic counseling and testing for BRCA mutation carriers. There was a high level of concern about cancer, recognition that community norms shift, acknowledgment of the role of the rabbi in medical decision making, and concern about the balance between determinism and personal responsibility in utilizing this health care service.

Conclusion:

The identification of social contributors to the utilization of genetic counseling and testing, as well as identification of solutions to optimize utilization of BRCA testing, supports the philosophic premise or conceptual model that faith-based leaders are crucial to the promotion of culturally sensitive health care delivery. Incorporating faith-based leaders early in health care strategic planning and implementation can translate into communities better utilizing health-related services.
Promise of Wearable Physical Activity Monitors in Oncology Practice
Authors: Beg Muhammad S. , Gupta Arjun , Stewart Tyler , Rethorst Chad D.
Published: February 2017

Commercially available physical activity monitors provide clinicians an opportunity to obtain oncology patient health measures to an unprecedented degree. These devices can provide objective and quantifiable measures of physical activity, which are not subject to errors or bias of self-reporting or shorter duration of formal testing. Prior work on so-called quantified-self data was based on older-generation, research-grade accelerometers, which laid the foundation for consumer-based physical activity monitoring devices to be validated as a feasible and reliable tool in patients with cancer. Physical activity monitors are being used in chronic conditions including chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, and obesity. Differing demographics, compounded with higher symptom and treatment burdens in patients with cancer, imply that additional work is needed to understand the unique strengths and weaknesses of physical activity monitors in this population. Oncology programs can systematically implement these tools into their workflows in an adaptable and iterative manner. Translating large amounts of data collected from an individual physical activity monitoring device into clinically relevant information requires sophisticated data compilation and reduction. In this article, we summarize the characteristics of older- and newer-generation physical activity monitors, review the validation of physical activity monitors with respect to health-related quality-of-life assessments, and describe the current role of these devices for the practicing oncologist. We also highlight the challenges and next steps needed for physical activity monitors to provide relevant information that can change the current state of oncology practice.
Xenopus laevis Kif18A is a highly processive kinesin required for meiotic spindle integrity
Authors: Möckel Martin M. , Heim Andreas , Tischer Thomas , Mayer Thomas U.
Published: February 2017

The assembly and functionality of the mitotic spindle depends on the coordinated activities of microtubule-associated motor-proteins of the dynein and kinesin superfamily. Our current understanding of the function of motor-proteins is significantly shaped by studies using Xenopus laevis egg extract as its open structure allows complex experimental manipulations hardly feasible in other model systems. Yet, the Kinesin-8 orthologue of human Kif18A has not been described in Xenopus laevis so far. Here, we report the cloning and characterization of Xenopus laevis (Xl) Kif18A. Xenopus Kif18A is expressed during oocyte maturation and its depletion from meiotic egg extract results in severe spindle defects. These defects can be rescued by wildtype Kif18A, but not Kif18A lacking motor-activity or the C-terminus. Single molecule microscopy assays revealed that Xl_Kif18A possesses high processivity, which depends on an additional C-terminal microtubule-binding site. Human tissue culture cells depleted of endogenous Kif18A display mitotic defects, which can be rescued by wildtype, but not tail-less Xl_Kif18A. Thus, Xl_Kif18A is the functional orthologue of human Kif18A whose activity is essential for the correct function of meiotic spindles in Xenopus oocytes.
Understanding the role of serotonin in psychiatric diseases
Authors: Marazziti Donatella
Published: February 2017

Serotonin (5-HT) continues to attract researchers’ interest after almost a century. However, despite these efforts, its role has not yet been fully elucidated. It is now evident that 5-HT does not modulate single functions but rather a multiplicity of activities and behaviors present in both normal and several pathological conditions in a less deterministic way than previously assumed. This article aims to briefly review some of the latest advancements in the general role of 5-HT in psychiatry, particularly in depression, and offer the author’s personal reflections.
A cross sectional study to determine the prevalence and risk factors of low back pain among public technical institute staff in Kurdistan Region, Iraq
Authors: Khudhir Karwan Mahmood , Mahmood Kochr  Ali , Saleh Kochar Khasro , Hossain Mosharaf
Published: February 2017

There is a lack of quantitative data regarding exposure response relationships between low back pain (LBP) and associated risk factors among institute staff in Kurdistan Region, Iraq. This study explored such associations in an analytic cross-sectional study. Data collection was carried out with a self-administered questionnaire. A total of 70 (90%) institute staff from Koya Technical Institute (KTI) participated in this study. The findings indicated that 61.4% of KTI staff report LBP. Independent variables significantly associated with reporting LBP (P value <0.05) during past 12 months were smoking (OR=10.882; 95%CI=1.301-90.995) and job tenure (OR=3.159; 95% CI=1.072-9.312). In conclusion, LBP is significantly associated with smoking and years worked; therefore, workers should be educated on the effects of smoking not only as it relates to LBP, but also how it affects the whole body and how to quit it. This can be done through health promotion campaigns and programs sponsored by the university.
Case Report: Emergency awake craniotomy for cerebral abscess in a patient with unrepaired cyanotic congenital heart disease
Authors: D’Antico Corinne , Hofer André , Fassl Jens , Tobler Daniel , Zumofen Daniel , Steiner Luzius A. , Goettel Nicolai
Published: February 2017

We report the case of a 39-year-old male with complex cyanotic congenital heart disease undergoing emergency craniotomy for a cerebral abscess. Maintenance of intraoperative hemodynamic stability and adequate tissue oxygenation during anesthesia may be challenging in patients with cyanotic congenital heart disease. In this case, we decided to perform the surgery as an awake craniotomy after interdisciplinary consensus. We discuss general aspects of anesthetic management during awake craniotomy and specific concerns in the perioperative care of patients with congenital heart disease.
Managerial Incentives and IT Strategic Posture
Authors: Xue Ling , Ray Gautam , Zhao Xia
Published: February 2017

This study examines how managerial incentives may drive firms to adopt a proactive strategic posture to implement more information technology (IT) than competitors. We consider both performance incentives that motivate managers to enhance firm returns and risk incentives that motivate managers to take risks. Our empirical analysis shows that while the proactiveness in IT strategic posture leads to both firm returns and firm risk, risk incentives rather than performance incentives essentially drive the proactiveness in IT strategic posture. These findings highlight the issue of managerial risk aversion and the important role of risk incentives in strategic IT decisions. Our study also shows that in diversified firms, risk incentives have a stronger marginal impact on the proactiveness in IT strategic posture in secondary business areas than in primary business areas. Performance incentives, however, may even generate a negative marginal impact on the proactiveness in IT strategic posture in secondary business areas. These results generate important implications for corporate owners regarding how to use various managerial incentives to motivate strategic IT decisions.

The online appendix is available at https://doi.org/10.1287/isre.2016.0660 .
Maintaining Beliefs in the Face of Negative News: The Moderating Role of Experience
Authors: Staats Bradley R. , KC Diwas S. , Gino Francesca
Published: February 2017

Many models in operations management involve dynamic decision making that assumes optimal updating in response to information revelation. However, behavioral theory suggests that rather than updating their beliefs, individuals may persevere in their prior beliefs. In particular, we examine how individuals’ prior experiences and the experiences of those around them alter their belief perseverance in operational decisions after the revelation of negative news. We draw on an exogenous announcement of negative news by the Food and Drug Administration and explore how it affects interventional cardiologists deciding between two types of cardiac stents. Analyzing 147,000 choices over six years, we find that individuals do respond to negative news by using the focal production tool less often. However, we find that both individuals’ own experiences and others’ experiences alter their responses. Moreover, although individual and other experience act as substitutes before negative news, we find that this substitution significantly curtails following the negative announcement. Finally, we find that experience leads doctors to discount negative news more rapidly over time. Two lab studies replicate our main findings and show that behavioral biases due to differences in perceptions of expertise drive the effect. Our research contributes not only to operations research but also to the practice of healthcare and operations.

The online appendix is available at https://doi.org/10.1287/mnsc.2016.2640 .

This paper was accepted by Serguei Netessine, operations management.
Developing an e-learning resource for nurse airway assistants in the emergency department
Authors: Hersey Peter , McAleer Sean
Published: February 2017

The aims of this project were to determine the required competencies for a nurse in the emergency department assisting with a rapid sequence induction of anaesthesia (RSI), and to produce a relevant e-learning resource. A three-round multidisciplinary Delphi process produced the following competencies: ability to describe the steps and sequence of events of an RSI, familiarity with the equipment used during an RSI, ability to recognise and help manage problems occurring during an RSI, ability to prepare for an RSI, ability to apply cricoid pressure, and understanding the modification of an RSI in special circumstances. An interactive e-learning package was produced and made available online. Twelve emergency department nurses took part in an evaluation of the e-learning package. All either agreed or strongly agreed that they had increased their knowledge and found the learning useful, and 11 out of 12 nurses reported being somewhat or very confident in the role of airway assistant following completion of the learning.
Making retention strategies work
Authors: Foster Sam
Published: February 2017

Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, discusses the retention of nurses and examines the evidence available that reveals the root of the problem and possible solutions
Supporting the psychological needs of teenagers and young adults during cancer treatment: a literature review
Authors: Hughes Natasha , Williams Julia , Shaw Carole
Published: February 2017

Background:

The developmental period of the teenage years and young adulthood can be a challenging time for most. Experiencing a diagnosis of cancer during this time inevitably presents further challenges and concerns. Identifying such issues can help to provide better ways of understanding the patients' experience and their needs, offering nurses insight to enhance care and support for teenagers and young adults (TYAs) undergoing cancer treatments.

Aim:

To explore the literature regarding the psychological issues faced by TYAs during cancer treatment to inform nursing practice.

Method:

A systematic search of electronic databases was conducted using predetermined search terms which yielded relevant articles. Applying an inclusion and exclusion criteria identified six articles that were deemed appropriate to explore the focus question.

Results:

A thematic analysis identified three main themes and five sub-themes: anxieties about treatment, concerns regarding the impact on life (feeling restricted and different, the benefits of being sick, facing uncertainty) and coping strategies (positive thinking and problem solving, support).

Conclusion:

Teenagers and young adults face a unique set of psychological concerns and challenges during cancer treatment, resulting in the development of specific coping strategies. These strategies should be promoted by nurses, ensuring patients are supported throughout their cancer journey.
Why bond market couldnâ€™t thrive in Pakistan
Authors: Rehman Seema , Khilji Jameel Ahmed
Published: February 2017

Fixed income market has recently emerged in Pakistan. Onward 1990, prolusion of government securities paved a way for corporates to come forward with their debt papers and long term yield curve came in to existence by introducing FIBâ€™s in 1992 followed by issuance of first Term Finance Certificates (TFC) in 1995. The TFCsâ€™ coupon rate exhibits a wide range of different fixed and floating coupons related to numerous interest rates containing the discount rate, the Karachi Inter-bank Offer Rate (KIBOR) and Pakistan Investment Bond (PIB) rates. The SBP launched electronic trading platform for fixed income securities on 11th January, 2010 with the intention of improving the functioning and profundity of primary and secondary markets of sovereign bonds. The data available reveals that through this platform, the cumulative trading of sovereign securities touched 66% of the overall trading volume till the end of 2010 relative to 58.0% in January, 2010. In its initial stage, the E-bond platform provided the complete trading of sovereign bonds like T-bills, PIBs and Ijarah Sukuk. The other type of fixed income securities like repo, FRAs and swaps facilitated in subsequent phases.
Natural products in green-detection of cancer cells, cancer therapy, and monitoring of therapeutic and cancer progression: A perspective
Authors: Islam Muhammad
Published: February 2017

The natural products embedded with the molecular framework by combining with themselves or other molecules and biological micro/macro molecules. By the help of some special techniques, that can be incorporated to identify and detect different body markers as well as pathophysiological conditions. To date, a number of cancer detection methods are available. However, an early cancer detection is still remained the key problems, which causes delay, reduction of success rate in the cancer therapy, and increased the lethality, as cancer is a complicated and a large group of related diseases. To date, due to the promising biological compatibility and safety profile, many natural products have been used as anticancer drugs. Additionally, many of them are also included in the green syntheses, especially the plant-derived products. It is due their less or even non-toxic and economic character. This text offers a perspective on the detection of cancer by using natural products, along with a therapeutic and monitoring of treatment and cancer progression, suggests that, the natural products can be considered as leading tools in overall cancer management.
Quantitative Analysis Method for Tencel A100 and Viscose Fiber Mixtures
Authors: Liu Jinrui , Gao Youjun , Zhang Xiangli , Zhao Sumin
Published: February 2017

This paper presents a quantitative analysis method for determining Tencel A100 (lyocell) fiber and viscose fiber content, and that of their blends, using a formic acid/zinc chloride dissolution procedure. Ultrasonic treatment was used in this procedure. A standard curve was generated to measure fiber content. This minimized errors caused by laboratory temperature changes, reagents and instruments used, and human factors.