Incorporating Integrated Personalised Diabetes Management (iPDM) in Treatment Strategy: A Pragmatic Approach.

Diabetes is a global public health concern. Vigilant monitoring and effective management of glycaemic variations are essential to prevent complications of diabetes. Effectively incorporating monitoring strategies in management of diabetes is a serious challenge. Patient-centered approach is necessary to customise monitoring and therapy of diabetes. This has been made possible by integrating technology with personalised therapeutic strategy. The integrated personalised diabetes management (iPDM) is a holistic, patient-centered approach that focuses on personalising diabetes management to streamline therapy and improve outcome. iPDM helps strengthen the care process, facilitates communication between patients and their healthcare team, and integrates digital tools that visualise and analyse data. The five E's which includes enthusiasm, education, expertise, empathy and engagement are the key pillars of a strong foundation for the iPDM model. iPDM model is a convenient and easily accessible tool that shifts the management paradigm from an "algorithmic" to "personalized" care to optimise treatment outcomes. Structured self-monitoring of blood glucose (SMBG) should be available as part of the self-management process for people with sub-optimally controlled type 2 diabetes, including those not on insulin therapies. Different SMBG regimens should be followed based on factors such as diabetes type, treatment approach (diet, oral antidiabetic medication, or insulin), glycaemic control, available resources, and patient's level of education.

An Expert Group Consensus Statement on "Approach and Management of Prediabetes in India".

The prevalence of prediabetes, a forerunner of diabetes is very high, and its conversion to diabetes is also more rapid among Asian Indians. Prediabetes also predisposes to the development of macrovascular and to a lesser extent of microvascular complications of diabetes. In a large community-based epidemiological study, the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB), data reported an overall prevalence of prediabetes of 10.3%, derived from 15 Indian states. This shows that the diabetes epidemic is far from over as many of them may soon convert to diabetes. Prediabetes, however, should not be considered a path to diabetes rather it should be a window of opportunity for the prevention of diabetes. This early screening, detection, and treatment of prediabetes should be made a national priority. Several countries have introduced lifestyle programs to prevent diabetes and, when indicated, pharmacological intervention with metformin as well. This consensus statement outlines the approaches to screening and lifestyle and pharmacological management of prediabetes in Asian Indians.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

Current evidence for COVID-19 therapies: a systematic literature review.

Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively. In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation versus standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.

Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.

The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.

Cognitive outcomes of childhood primary CNS vasculitis.

OBJECTIVE: To characterize the clinical cognitive phenotypes and severity of cognitive burden according to disease subtype in children with primary central nervous system vasculitis (cPACNS). METHOD: This retrospective multicenter inflammatory brain disease database study examined the neuropsychological outcomes of 80 children (44 male; mean age = 7.89 years, SD = 4.17) consecutively diagnosed with primary CNS vasculitis between 1992 and 2016. Twenty-one children had small-vessel disease (AN_cPACNS), and 59 had large-vessel disease (including 49 nonprogressive [APNP_cPACNS] and 10 progressive [APP_cPACNS]). Neuroimaging revealed MRI abnormalities in 100% and 90% of children with large- and small-vessel vasculitis, respectively. The primary outcomes were Full Scale IQ (FSIQ) and the index scores from the Wechsler Intelligence Scale for Children-III (WISC-III, WISC-IV, and WISC-V). Analyses explored the effect of disease subtype. RESULTS: Intellectual functioning was assessed on average 2.82 years after symptom onset. Children with small-vessel CNS vasculitis had significantly lower FSIQ scores than did those with large-vessel CNS vasculitis (Ms = 81.90 vs. 94.82; p = .04). Intellectual disability (FSIQ < 70) was more frequent in children with small-vessel disease (24% vs. 5%). All groups displayed lower Working Memory and Processing Speed index scores relative to Verbal Comprehension and Perceptual Reasoning index scores. Group differences in FSIQ remained significant after controlling for the presence of seizures. CONCLUSION: Children with small-vessel CNS vasculitis are more likely to demonstrate deficits in intellectual functioning than are those with large-vessel disease, and children with both types of CNS vasculitis demonstrate relatively poor working memory and processing speed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Health-related quality of life in children with inflammatory brain disease.

OBJECTIVE: To quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning. METHODS: This was a multicenter, observational cohort study of children (< 18 years of age) diagnosed with inflammatory brain disease (IBrainD). Patients were included if they had completed at least one Health Related Quality of Life Questionnaire (HRQoL). HRQoL was measured using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL) Generic Core Scales, which provided a total score out of 100. Analyses of trends were performed using linear regression models adjusted for repeated measures over time. RESULTS: In this study, 145 patients were included of which 80 (55%) were females. Cognitive dysfunction was the most common presenting symptoms (63%), and small vessel childhood primary angiitis of the CNS was the most common diagnosis (33%). The mean child's self-reported PedsQL total score at diagnosis was 68.4, and the mean parent's proxy-reported PedsQL score was 63.4 at diagnosis. Child's self-reported PedsQL scores reflected poor HRQoL in 52.9% of patients at diagnosis. Seizures or cognitive dysfunction at presentation was associated with statistically significant deficits in HRQoL. CONCLUSION: Pediatric IBrainD is associated with significantly diminished health-related quality of life. Future research should elucidate why these deficits occur and interventions should focus on improving HRQoL in the most affected subdomains, in particular for children presenting with seizures and cognitive dysfunction.

Childhood Takayasu arteritis: disease course and response to therapy.

BACKGROUND: Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome. METHODS: A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit. OUTCOME: disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death. ANALYSIS: logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens. RESULTS: Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease (p = 0.02). No additional outcome predictor was identified. CONCLUSIONS: Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity.

Distinct phenotype clusters in childhood inflammatory brain diseases: implications for diagnostic evaluation.

OBJECTIVE: To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. METHODS: A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. RESULTS: A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. CONCLUSION: Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted.

Childhood primary angiitis of the central nervous system: identifying disease trajectories and early risk factors for persistently higher disease activity.

OBJECTIVE: To compare clinical, laboratory, and imaging characteristics of childhood primary angiitis of the central nervous system (PACNS) subtypes at diagnosis and during followup; to characterize disease activity trajectories in childhood PACNS subtypes; and to identify early risk factors for higher disease activity. METHODS: We performed a single-center cohort study of consecutive children diagnosed as having childhood PACNS. Demographic, clinical, laboratory, and imaging data were collected at diagnosis and during standardized clinic visits. Outcome measures included disease activity measured by physician's global assessment. Descriptive statistics were used to assess characteristics of the study cohort, and longitudinal data were analyzed using linear mixed-effects regression. RESULTS: The study cohort consisted of 45 patients with childhood PACNS; 26 had angiography-negative childhood PACNS and 19 had angiography-positive childhood PACNS. There were 24 females, the median age at diagnosis was 9.8 years, and the median followup period was 1.8 years. Patients with angiography-negative childhood PACNS were more likely to be female and to present with seizures, cognitive dysfunction, vision abnormalities, high levels of inflammatory markers, and bilateral findings on magnetic resonance imaging (MRI). Motor deficits and ischemic MRI lesions were more common in angiography-positive disease. Disease activity decreased significantly after treatment in all patients. Distinct trajectories of disease activity over time were identified for both childhood PACNS subtypes. Patients with angiography-negative childhood PACNS had persistently higher disease activity. Seizures at presentation also predicted higher disease activity over time. CONCLUSION: Distinct subtypes of childhood PACNS have unique disease activity trajectories. Patients with angiography-negative disease and seizures at presentation experience higher disease activity. Early recognition of this high-risk cohort may enable the treating physician to initiate targeted therapies and prevent long-term brain injury.

CIMP status of interval colon cancers: another piece to the puzzle.

OBJECTIVES: Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers. METHODS: We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI. RESULTS: There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.01-3.8), MSI (OR 2.7; 95% CI 1.1-6.8) and CIMP (OR 2.41; 95% CI 1.2-4.9) were independently associated with interval cancers. CIMP was associated with interval cancers independent of MSI status. There was no difference in 5-year survival between the two groups. CONCLUSIONS: Interval cancers are more likely to arise in the proximal colon and demonstrate CIMP, which suggests there may be differences in biology between these and non-interval CRC. Additional studies are needed to determine whether interval cancers arise as a result of missed lesions or accelerated neoplastic progression.