Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade.

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.

Oral healthcare seeking behavior of Malaysian adults in urban and rural areas: findings from the National Health and Morbidity Survey 2019.

BACKGROUND: The development and implementation of appropriate strategies to enhance oral health in the community can be aided by an understanding of oral healthcare seeking behavior among urban and rural populations. The purpose of this study was to identify the factors associated with oral healthcare seeking behavior of the Malaysians in urban and rural locations who self-reported dental problems. METHODS: The National Health and Morbidity Survey 2019, a cross-sectional nationwide household survey that focused on non-institutionalised Malaysians, provided the data for this study on adults in Malaysia who were 18 years of age and older. A two-stage stratified random sampling technique was employed to ensure national representativeness. Data was collected using a multilingual (Malay and English), structured, and validated questionnaire via face-to-face interviews from July to October 2019. The dependent variable was oral healthcare seeking behavior (sought oral healthcare and self-medication). Independent variables were predisposing, enabling and health needs factor based on Andersen's Behavioral Model. Descriptive statistics were used to describe the characteristics and oral healthcare seeking behavior of the respondents. The relationship between the independent and dependent variables were investigated using multivariable logistic regression analysis. RESULTS: The analysis comprised a total of 10,134 respondents, representing about 18.2 million Malaysian adults aged 18 and above. The overall prevalence of Malaysian adults who self-reported dental problems was low (5.5%) and was slightly higher in the rural than urban population. Almost half sought treatment from healthcare practitioners, and almost a quarter self-medicated. Ethnicity was associated with seeking healthcare and self-medication among urban dwellers. Among the rural population, income level was associated with seeking healthcare while education level was associated with self-medication. CONCLUSION: Disparities in oral healthcare seeking behaviors exist between Malaysians living in urban and rural areas. Future policies should adopt focused strategies that concentrate on oral healthcare accessibility and health literacy of the vulnerable and rural populations to achieve the best oral healthcare for this population group.

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

The Health-Seeking Behavior among Malaysian Adults in Urban and Rural Areas Who Reported Sickness: Findings from the National Health and Morbidity Survey (NHMS) 2019.

Understanding care-seeking behavior among urban and rural populations can help to support the planning and implementation of appropriate measures to improve health in the community. This study aims to determine the factors associated with the health-seeking behavior among Malaysian adults in urban and rural areas who reported sickness. This study used data of Malaysian adults aged 18 years and over from the National Health and Morbidity Survey 2019; a cross-sectional, national household survey that targeted all non-institutionalized residents in Malaysia. Respondent's characteristics and health-seeking behavior were described using complex sample descriptive statistics. Multivariable logistic regression analysis was conducted to examine the association between potential factors (sociodemographic characteristics, enabling, and health need) and health-seeking behaviors (seeking treatment from healthcare practitioners and self-medication). A total of 10,484 respondents, estimated to represent 18.9 million Malaysian adults aged 18 years and over, were included in the analysis. Prevalence of seeking treatment from healthcare practitioners and self-medication among Malaysian adults with self-reported sickness were 57.3% and 23.3%, respectively. Self-reported sickness among both the urban and rural populations who rated their health as poor to very poor was more likely to seek treatment than those who rated good to excellent. However, among the urban population, those who rated their health as poor to very poor were less likely to self-medicate. Among the urban population, government employees were more likely to seek treatment, and being without formal education significantly increased the likelihood to self-medicate. Among the rural population, those with at least one long-term condition were more likely to seek treatment than those with none. Understanding the factors which influence health-seeking behavior among the urban and rural population could close the gaps in healthcare utilization among the population in Malaysia.

SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC). PATIENTS AND METHODS: We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME. RESULTS: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]. CONCLUSIONS: SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.

Determinants of community pharmacy utilisation among the adult population in Malaysia: findings from the National Health and Morbidity Survey 2019.

BACKGROUND: Community pharmacies provide alternatives for medication procurement and other basic and minor health-related services in addition to mainstream hospitals and primary healthcare services. This study aimed to determine the characteristics of community pharmacy users and associated factors for community pharmacy utilisation in Malaysia. METHODS: Secondary data analysis was performed using data from the National Health and Morbidity Survey 2019, a nationwide cross-sectional household survey that used a two-stage stratified random sampling design. Adults aged 18 years and over were included in the analysis. Respondents who reported visiting the community pharmacy for health purposes two weeks prior to the study were considered as users. Complex sample descriptive statistics were used to describe the respondents' characteristics. Logistic regression analyses were employed to determine factors associated with community pharmacy utilisation. RESULTS: Of the 11,155 respondents interviewed, 10.3 % reported community pharmacy utilisation for health purposes. Females (OR = 1.41, 95 % CI = 1.14, 1.73), those with tertiary education (OR = 2.03, 95 % CI = 1.26, 3.29), urban dwellers (OR = 1.42, 95 % CI = 1.13, 1.79), and those with self-reported health problems (OR = 7.62, 95 % CI = 6.05, 9.59) were more likely to utilise the community pharmacy. CONCLUSIONS: Demographic and socioeconomic factors were important determinants of community pharmacy utilisation in Malaysia with sex, age, education level, locality, and self-reported health problems as the associated factors. These findings serve as evidence for policy interventions, crucial for improvements in accessibility to healthcare services.

The impacts of caregiving intensity on informal caregivers in Malaysia: findings from a national survey.

BACKGROUND: Provision of informal care may adversely affect health, daily and social activities of the informal caregivers, but few studies have examined these effects in relation to caregiving intensity. This study examined the predictive factors associated with the effects of caregiving roles on health, daily and social activities of informal caregivers, accounting for caregiving intensity. METHODS: Data of adults aged 18 years and over from the National Health and Morbidity Survey 2019 were used. Respondent's demographic, socioeconomic, health, and caregiving-related characteristics were described using complex samples analysis. Logistic regression analysis was performed to examine the factors affecting health, daily and social activities of caregivers, accounting for caregiving intensity. RESULTS: Five point one percent of adults in Malaysia provided informal care. High intensity caregivers were more likely to be actively employed and provided longer duration of care compared with low intensity caregivers. For low intensity caregiving, females, those aged 35-59 years, and those with long-term condition were more likely to have negative effects on health. Daily activities of non-Malays were more likely to be affected, while no factor was found significantly associated with effect on social activities. For high intensity caregiving, caregivers aged 60 and over, those received training and those without assistance were more likely to have negative effects on health. Daily activities of those without assistance were more likely to be affected. Social activities of non-Malays, those received training and those providing care for 2 years or more were more likely to be affected. CONCLUSIONS: Our study indicates that both low- and high-intensity caregivers have common features, with the exception of employment status and care duration. Caregiving, regardless of intensity, has a significant impact on caregivers. In order to reduce the negative consequences of caregiving responsibilities, all caregivers need assistance from the community and government, that is customised to their needs. By addressing the factors contributing to the negative effects of caregiving, a continuation of informal caregiving can be sustained through policies supporting the growing demand for informal care necessitated by an ageing population and higher life expectancy in Malaysia.

Demographic and socioeconomic inequalities in oral healthcare utilisation in Malaysia: evidence from a national survey.

BACKGROUND: Throughout the years, oral healthcare utilisation in Malaysia has been low despite various efforts by the Ministry of Health Malaysia for improvement. This study aimed to determine the prevalence of oral healthcare utilisation and identify factors associated with oral healthcare utilisation among adults in Malaysia. METHODS: Secondary data analysis of adults aged 18 years and over from the National Health and Morbidity Survey 2019 was conducted in this study. Characteristics of respondents and those who utilised oral healthcare were described using complex sample descriptive statistics. Logistic regression analysis was performed to examine the association between the dependent and independent variables. Dependent variable was oral healthcare utilisation in the last 12 months. Independent variables were demographic and socioeconomic factors (predisposing, enabling and need characteristics) based on Andersen's Behavioural Model. RESULTS: A total of 11,308 respondents, estimated to represent 21.7 million adults aged 18 years and over in Malaysia were included in the analysis. Prevalence of oral healthcare utilisation in the last 12 months was 13.2%. Demographic factors of sex, age, marital status, and socioeconomic factors of education level and occupation as well as health belief such as medical check-up were significantly related to oral healthcare utilisation. Enabling factor of household income quintile had significant association with oral healthcare utilisation. Inequalities were observed; females (OR = 1.57, 95% CI = 1.25, 1.96), younger adults (OR = 1.64, 95% CI = 1.15, 2.33), those who were married (OR = 1.65, 95% CI = 1.23, 2.22), those with higher education (OR = 2.21, 95% CI = 1.23, 3.99), those who had medical check-up in the last 12 months (OR = 1.86, 95% CI = 1.53, 2.25) and those with higher income (OR = 1.43, 95% CI = 1.04, 1.96) were more likely to utilise oral healthcare. CONCLUSION: Understanding factors associated with utilisation of oral healthcare could help in formulating effective interventions to improve oral healthcare utilisation. Demographic and socioeconomic factors are strong determinants of oral healthcare utilisation in Malaysia. Appropriate interventions to strengthen the existing programmes aimed to promote regular and timely oral health check-ups are needed to improve oral healthcare utilisation.

A microfluidic platform for functional testing of cancer drugs on intact tumor slices.

Present approaches to assess cancer treatments are often inaccurate, costly, and/or cumbersome. Functional testing platforms that use live tumor cells are a promising tool both for drug development and for identifying the optimal therapy for a given patient, i.e. precision oncology. However, current methods that utilize patient-derived cells from dissociated tissue typically lack the microenvironment of the tumor tissue and/or cannot inform on a timescale rapid enough to guide decisions for patient-specific therapy. We have developed a microfluidic platform that allows for multiplexed drug testing of intact tumor slices cultured on a porous membrane. The device is digitally-manufactured in a biocompatible thermoplastic by laser-cutting and solvent bonding. Here we describe the fabrication process in detail, we characterize the fluidic performance of the device, and demonstrate on-device drug-response testing with tumor slices from xenografts and from a patient colorectal tumor.

Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

Biological disease-modifying antirheumatic drugs in juvenile idiopathic arthritis of polyarticular course, enthesitis-related arthritis, and psoriatic arthritis: a consensus statement.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common type of inflammatory arthritis in children. Treatment options have been expanded since the introduction of biologics, which are highly effective. The existing local JIA treatment guideline was published more than a decade ago, when use of biologics was not as common. In this article, we review the latest evidence on using biologics in three JIA subtypes: JIA of polyarticular course (pcJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). Based on the latest information, an update on eligibility, response assessment, termination, and safety information for using biologics in these patients was performed. CONSENSUS PROCESS: The JIA Work Group, which consisted of nine paediatricians experienced in managing JIA, was convened in 2016. Publications before July 2017 were screened. Eligible articles were clinical trials, extension studies, systemic reviews, and recommendations from international societies and regulatory agencies about the use of biologics in pcJIA, ERA, and PsA. Evidence extraction, appraisal, and drafting of propositions were performed by two reviewers. Extracted evidence and drafted propositions were presented and discussed at the first two meetings. Overwhelming consensus was obtained at the final meeting in May 2018. Seven practice consensus statements were formulated. Regular review should be performed to keep the practice evidence-based and up-to-date.

Elevated fasting vs post-load glucose levels and pregnancy outcomes in gestational diabetes: a population-based study.

AIMS: To examine the relative association between fasting plasma glucose vs post-load (1-h and 2-h) glucose levels based on the oral glucose tolerance test in pregnancy and large-for-gestational-age and hypertensive disorders of pregnancy outcomes. METHODS: All live singleton births between October 2008 and December 2014 in Alberta, Canada were included. Gestational diabetes mellitus was diagnosed using Diabetes Canada criteria. Logistic regression models were used to examine the association between fasting plasma glucose vs post-load values and large-for-gestational-age infants and hypertensive disorders of pregnancy after adjusting for maternal characteristics and pharmaceutical intervention in gestational diabetes pregnancies. RESULTS: Among 257 547 pregnancies, 208 344 (80.9%) had negative 50-g glucose challenge tests, 36 261 (14.1%) had negative 75-g oral glucose tolerance tests, and 12 942 (5.0%) had gestational diabetes based on either elevated fasting plasma glucose (n=4130, 1.6%) or elevated 1-h and/or 2-h oral glucose tolerance test values (n=8812, 3.4%). Large-for-gestational-age and hypertensive disorders of pregnancy rates were 8.1% and 5.1% in negative glucose challenge test pregnancies, 11.0% and 7.0% in negative oral glucose tolerance test pregnancies, 22.4% and 11.9% in gestational diabetes pregnancies with elevated fasting plasma glucose, and 9.1% and 8% in gestational diabetes pregnancies with elevated post-load levels, respectively. Among gestational diabetes pregnancies, those with elevated fasting plasma glucose were at higher risk of large-for-gestational age (adjusted odds ratio 2.66, 95% CI 2.39-2.96) and hypertensive disorders of pregnancy (adjusted odds ratio 1.51, 95% CI 1.33-1.72) outcomes relative to pregnancies with post-load glucose elevations only. Fasting plasma glucose remained significantly associated with adverse outcomes in gestational diabetes pregnancies with and without pharmacological intervention. CONCLUSIONS: Elevated fasting plasma glucose in women with gestational diabetes is a stronger predictor of large-for-gestational-age and hypertensive disorders of pregnancy outcomes than elevated post-load glucose.

Stereotactic Body Radiotherapy for Small Unresectable Hepatocellular Carcinomas.

AIMS: Stereotactic body radiotherapy (SBRT) is an option for the treatment of hepatocellular carcinoma (HCC) in patients ineligible for standard local therapies. This study reports on the safety and efficacy of SBRT in small HCC tumours (≤5 cm) in the province of British Columbia. MATERIALS AND METHODS: Between March 2011 and July 2015, 31 patients with Child-Pugh Class A or B, with small HCCs measuring ≤5 cm were treated with SBRT at our institution. Primary end points were local control, progression-free survival, overall survival and toxicity. RESULTS: Thirty-four hepatomas (median size 3.3 cm, range 1.3-5.0 cm) were treated. The median follow-up was 18.3 months. Twenty-six patients (84%) had received previous liver-directed treatments. Most patients (88%) were treated with 45 Gy in three or five fractions. Six patients (19%) had worsened Child-Pugh score by two or more points during follow-up; overall 32% of patients experienced ≥ grade 3 + toxicities. One-year local control and overall survival were 94 and 84%, respectively. One-year progression-free survival was 49%; 81% of patients with disease progression received further HCC therapy. On univariate analysis, small tumour size predicted for improved overall survival (P = 0.01) whereas prescription biological equivalent dose (BED10) ≥100Gy10 approached significance (P = 0.06). CONCLUSION: SBRT provides high local control to small inoperable HCC. SBRT can be delivered safely even after previous liver-directed therapies and further liver therapies can follow treatment with SBRT. Although overall 32% of patients experienced ≥ grade 3 + toxicities, and 19% had a deterioration in Child-Pugh score of two or more points, these changes were mainly transient with minimal clinical impact. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximise disease control.

Recommendations on prevention and screening for colorectal cancer in Hong Kong.

Colorectal cancer is the commonest cancer in Hong Kong. The Cancer Expert Working Group on Cancer Prevention and Screening was established in 2002 under the Cancer Coordinating Committee to review local and international scientific evidence, assess and formulate local recommendations on cancer prevention and screening. At present, the Cancer Expert Working Group recommends that average-risk individuals aged 50 to 75 years and without significant family history consult their doctors to consider screening by: (1) annual or biennial faecal occult blood test, (2) sigmoidoscopy every 5 years, or (3) colonoscopy every 10 years. Increased-risk individuals with significant family history such as those with a first-degree relative diagnosed with colorectal cancer at age ≤60 years; those who have more than one first-degree relative diagnosed with colorectal cancer irrespective of age at diagnosis; or carriers of genetic mutations associated with familial adenomatous polyposis or Lynch syndrome should start colonoscopy screening earlier in life and repeat it at shorter intervals.

Recommendations on prevention and screening for breast cancer in Hong Kong.

In Hong Kong, breast cancer is the most common cancer among women and poses a significant health care burden. The Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) was set up in 2002 by the Cancer Coordinating Committee to review and assess local and international scientific evidence, and to formulate recommendations for cancer prevention and screening. After considering the local epidemiology, emerging scientific evidence, and local and overseas screening practices, the CEWG concluded that it was unclear whether population-based breast cancer screening did more harm than good in local asymptomatic women at average risk. The CEWG considers that there is insufficient evidence to recommend for or against population-based mammography screening for such individuals. Women who consider breast cancer screening should be adequately informed about the benefits and harms. The CEWG recommends that all women adopt primary preventive measures, be breast aware, and seek timely medical attention for suspicious symptoms. For women at high risk of breast cancer, such as carriers of confirmed BRCA1/2 deleterious mutations and those with a family history of breast cancer, the CEWG recommends that they seek doctor's advice for annual mammography screening and the age at which the process should commence. Additional annual screening by magnetic resonance imaging is recommended for confirmed BRCA1/2 mutation carriers or women who have undergone radiation therapy to the chest between the age of 10 and 30 years. Women at moderate risk of breast cancer should discuss with doctors the pros and cons of breast cancer screening before making an informed decision about mammography screening every 2 to 3 years.

Emergency thrombectomy for acute ischaemic stroke: current evidence, international guidelines, and local clinical practice.

Acute ischaemic stroke due to large vessel occlusion leads to grave neurological morbidity and mortality. Conventional intravenous thrombolysis is ineffective in achieving timely reperfusion in this group of patients. The publication of five positive randomised controlled trials of emergency thrombectomy for acute ischaemic stroke in 2015 provided strong evidence to support endovascular reperfusion therapy and represented a paradigm shift in acute stroke management. In this article, we review the current evidence and international guidelines, and report on the findings of a survey study of the clinical practice and opinions of local neurologists, neurosurgeons, and interventional radiologists in emergency thrombectomy. We also discuss the controversies around thrombectomy treatment, local experience, and suggestions to incorporate thrombectomy in acute stroke treatment.

Patterns of glucose-lowering therapies and neonatal outcomes in the treatment of gestational diabetes in Canada, 2009-2014.

AIM: To examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus. METHODS: This was a large, retrospective, population-based cohort study of pregnant women with gestational diabetes from Alberta, Canada. We linked data from the Alberta Vital Statistics - Birth database with administrative claims data. Alberta Vital Statistics - Birth data were used to identify births that occurred between 1 January 2009 and 31 December 2014. We used International Classification of Diseases version 9/10 codes to identify women with gestational diabetes, and we excluded women with pre-existing diabetes. RESULTS: Our cohort consisted of 16 857 women with gestational diabetes, with a total of 18 761 birth events between 2009 and 2014. Over the study period, the proportion of women with gestational diabetes who were treated with glycaemic control therapies increased from 25.0% to 31.4% (P<0.0001). The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P<0.0001), as did the number treated with metformin, +/- insulin (from 1.4% to 3.2%; P<0.0001). Rates of large-for-gestational-age infants were significantly higher among pregnancies treated with insulin only (17%) or metformin (16.5%) than among pregnancies that did not receive any pharmacological treatment (12.8%). CONCLUSIONS: Our findings show increasing use of insulin and metformin in women with gestational diabetes. Rates of large-for-gestational-age infants were similar among pregnant women receiving either pharmacological treatment, and higher than among pregnant women who did not receive any pharmacological treatment. Future research should explore the long-term outcomes and safety of metformin as an alternative for treating gestational diabetes.

The Role of Radiotherapy in Epidermal Growth Factor Receptor Mutation-positive Patients with Oligoprogression: A Matched-cohort Analysis.

AIMS: Almost all patients with epidermal growth factor receptor (EGFR) mutations will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The management of oligoprogression on EGFR TKI is controversial. Irradiating progressing tumours may potentially eradicate the resistant clone and allow continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess the effect of radiotherapy on survival outcomes in patients with oligoprogression in a matched-cohort study. MATERIALS AND METHODS: This was a retrospective matched-cohort study comparing patients with EGFR mutation-positive stage IV non-small cell lung cancer receiving radiotherapy versus chemotherapy for progression. Patients in the radiotherapy group received radiotherapy (mainly stereotactic ablative radiotherapy) for oligoprogression, whereas the chemotherapy group received only systemic chemotherapy upon progression. Key prognostic factors including gender, age, performance status, time to first progression and mutation subtypes were matched. RESULTS: Twenty-five patients with oligoprogression (radiotherapy group) were identified, and a matched chemotherapy group with the same number of patients was generated. The median duration of follow-up was 24.3 and 34 months for the radiotherapy and chemotherapy groups, respectively. The median overall survival of the radiotherapy group was significantly longer than the chemotherapy group, 28.2 versus 14.7 months (P = 0.026). The median progression-free survival (PFS) was 7.0 and 4.1 months after radiotherapy and chemotherapy, respectively (P = 0.0017). The use of radiotherapy was an independent predictive factor of overall survival and PFS in multivariate analysis. Only one patient had ≥grade 3 toxicity after radiotherapy. The frequency of secondary T790M mutation and subsequent Osimertinib exposure were similar in both groups. CONCLUSION: Radiotherapy may effectively extend EGFR TKI therapy for patients with oligoprogression on TKI. Improved PFS and overall survival were observed, although potential biases should not be overlooked. Further randomised studies are warranted.

A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.

AIMS: To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).