Sponsored by OPRI with partial funding by Circassia and study drugs provided by TEVA.

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We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%–98.8%) and 80.9% (74.6%–81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%–98.5%), and 90.9% (50.8%–98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8–14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%–100%) and 80.3% (70.7%–89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%–94.1%) and 73.6% (67.2%–79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

PurposeAsthma is a global health problem, and asthma prevalence in Asia is increasing. The REcognise Asthma and LInk to Symptoms and Experience Asia study assessed patients’ perception of asthma control and attitudes toward treatment in an accessible, real-life adult Asian population.Patients and methodsAn online survey of 2,467 patients with asthma from eight Asian countries/regions, aged 18–50 years, showed greater than or equal to two prescriptions in previous 2 years and access to social media. Patients were asked about their asthma symptoms, exacerbations and treatment type, views and perceptions of asthma control, attitudes toward asthma management, and sources of asthma information.ResultsPatients had a mean age of 34.2 (±7.4) years and were diagnosed with asthma for 12.5 (±9.7) years. Half had the Global Initiative for Asthma-defined uncontrolled asthma. During the previous year, 38% of patients visited the emergency department, 33% were hospitalized, and 73% had greater than or equal to one course of oral corticosteroids. About 90% of patients felt that their asthma was under control, 82% considered their condition as not serious, and 59% were concerned about their condition. In all, 66% of patients viewed asthma control as managing attacks and 24% saw it as an absence of or minimal symptoms. About 14% of patients who correctly identified their controller inhalers had controlled asthma compared to 6% who could not.ConclusionPatients consistently overestimated their level of asthma control contrary to what their symptoms suggest. They perceived control as management of exacerbations, reflective of a crisis-oriented mind-set. Interventions can leverage on patients’ trust in health care providers and desire for self-management via a new language to generate a paradigm shift toward symptom control and preventive care.

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The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment. Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. .

IntroductionSingapore's rapidly ageing population and chronic disease burden at public hospital specialist clinics herald a silver tsunami. In Singapore, “right siting” aims to manage stable chronic disease in primary care at a lower cost. To improve the quality of rheumatology care, we created shared care between rheumatologist and family physician to reduce hospital visits.MethodsClinical practice improvement methodology was used to structure shared care of stable patients between hospital rheumatologists and eleven community family physicians; one ran a hospital clinic. A case manager coordinated the workflow.ResultsAbout 220 patients entered shared care over 29 months. Patients without hospital subsidies (private patients) and private family physicians independently predicted successful shared care, defined as one cycle of alternating care.DiscussionOur shared care model incorporated a case manager, systematic workflows, patient selection criteria, willing family physician partners and rheumatologists in the absence of organizational integration. Health care affordability impacts successful shared care. Government subsidy hindered right siting to private primary care.ConclusionsFinancing systems in Singapore, at health policy level, must allow transfer of hospital subsidies to primary care, both private and public, to make it more affordable than hospital care. Structural integration will create a seamless continuum between hospital and primary care.

Asthma is associated with a significant burden of disease, especially for patients with severe or uncontrolled asthma. Many patients with severe asthma still receive treatment in primary care settings and despite the availability of effective options, inadequate asthma treatment remains a concern, particularly the use of systemic corticosteroids to treat exacerbations and severe asthma. Around the world, many patients are stuck in a vicious circle of misdiagnosis, undertreatment, and poor understanding of disease severity and management. In this manuscript, we describe the development of The Asthma Referral Identifier (ReferID) tool, a simple, 4-item questionnaire that healthcare providers can use to help identify patients with uncontrolled and/or potentially severe asthma. ReferID was developed specifically for use in primary care clinics in low- and middle-income countries and other clinics, where the optimisation of asthma assessments and treatment recommended for countries with well-established healthcare systems, are not possible. ReferID was developed through an informal collaborative process involving international asthma experts as well as general practitioners, nurses, and specialists throughout the Asia Pacific, Latin America and Middle East regions, in conjunction with current evidence and treatment guidelines. In collaboration with local and regional partners around the world, the developers have adapted ReferID and translated it into 21 languages, and implementation is ongoing in 30 countries. ReferID has the potential to help break the vicious circle, improving disease outcomes and health-related quality of life for patients with asthma.