Background Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor ...control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. Methods and findings This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization angioplasty or coronary artery bypass graft), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 intervention; n = 437 usual care). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval CI, 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% 95% CI: −13.2, −1.7, p = 0.01; hazard ratio HR = 0.72 95% CI: 0.61, 0.86), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. Conclusions In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. Trial registration ClinicalTrials.gov NCT01212328 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2.
Comprehensive diabetes care: The Goa model Desai, Ankush K; Usgaonkar, Ugam P S; Naik, Vivek S ...
Indian journal of ophthalmology,
02/2020, Letnik:
68, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
Diabetes mellitus continues to increase in epidemic proportions globally as well as in India. Poor glycemic control in long-standing diabetes mellitus eventually leads to chronic complications such ...as retinopathy, nephropathy, neuropathy, and cardiovascular disease. Diabetic retinopathy is emerging as an important cause of avoidable visual impairment and blindness in India across all strata of society. Much of this vision loss can be prevented by improving control of known risk factors, annual fundus screening, with prompt treatment of individuals with sight-threatening retinopathy. The Queen Elizabeth Diamond Jubilee Trust has made a significant contribution by supporting such a program across India, including Goa. The newly established medical retina clinic at Goa Medical College now provides facilities for screening, a detailed evaluation of advanced retinopathy, and therapeutic modalities such as laser and intravitreal injections. The peripheral centers are equipped to screen all people with diabetes mellitus and refer those with sight-threatening retinopathy to the medical college. The provision of a foot scanner to evaluate the risk of foot ulcers and microalbuminuria assessment as part of the nephropathy screening would encompass the entire gamut of diabetic microvascular complications. The next decade would provide evidence if this initiative, with the enthusiastic partnership of the state government, results in reduction of blindness in the people of Goa and an overall reduction in diabetes-related morbidity and mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionThe development of type 2 diabetes mellitus disproportionately affects South Asian women with prior gestational diabetes mellitus (GDM). The Lifestyle InterVention IN Gestational diabetes ...(LIVING) Study is a randomised controlled trial of a low-intensity lifestyle modification programme tailored to women with previous GDM, in India, Bangladesh and Sri Lanka, aimed at preventing diabetes/pre-diabetes. The aim of this process evaluation is to understand what worked, and why, during the LIVING intervention implementation, and to provide additional data that will assist in the interpretation of the LIVING Study results. The findings will also inform future scale-up efforts if the intervention is found to be effective.Methods and analysisThe Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) methodological approach informed the evaluation framework. Michie’s Behaviour Change Theory and Normalisation Process Theory were used to guide the design of our qualitative evaluation tools within the overall RE-AIM evaluation framework. Mixed methods including qualitative interviews, focus groups and quantitative analyses will be used to evaluate the intervention from the perspectives of the women receiving the intervention, facilitators, site investigators and project management staff. The evaluation will use evaluation datasets, administratively collected process data accessed during monitoring visits, check lists and logs, quantitative participant evaluation surveys, semistructured interviews and focus group discussions. Interview participants will be recruited using maximum variation purposive sampling. We will undertake thematic analysis of all qualitative data, conducted contemporaneously with data collection until thematic saturation has been achieved. To triangulate data, the analysis team will engage in constant iterative comparison among data from various stakeholders.Ethics and disseminationEthics approval has been obtained from the respective human research ethics committees of the All India Institute of Medical Sciences, New Delhi, India; University of Sydney, New South Wales, Australia; and site-specific approval at each local site in the three countries: India, Bangladesh and Sri Lanka. This includes approvals from the Institutional Ethics Committee at King Edwards Memorial Hospital, Maharaja Agrasen Hospital, Centre for Disease Control New Delhi, Goa Medical College, Jawaharlal Institute of Postgraduate Medical Education and Research, Madras Diabetes Research Foundation, Christian Medical College Vellore, Fernandez Hospital Foundation, Castle Street Hospital for Women, University of Kelaniya, Topiwala National Medical College and BYL Nair Charitable Hospital, Birdem General Hospital and the International Centre for Diarrhoeal Disease Research. Findings will be documented in academic publications, presentations at scientific meetings and stakeholder workshops.Trial registration numbersClinical Trials Registry of India (CTRI/2017/06/008744); Sri Lanka Clinical Trials Registry (SLCTR/2017/001) and ClinicalTrials.gov Registry (NCT03305939); Pre-results.
Objectives
To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with ...gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria.
Methods
This post‐hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria.
Results
We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow‐up period of 1.8 (1.4–2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6–10.0)/100 women‐years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval CI, 1.18–2.54; p = .005) and 3.56 (95% CI, 2.46–5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70–4.00; p < .001), compared to isolated abnormal FPG.
Conclusions
Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.
Highlights
Of the 1468 South Asian women with gestational diabetes, 213 (14.5%) women developed diabetes over median follow‐up 1.8 years after childbirth, an incidence rate of 8.7/100 women‐years.
The incidence rates for participants with any one, two, and three abnormal values on antenatal oral glucose tolerance test (OGTT) were 4.3, 8.3 and 19.0/100 women years.
The rates of future diabetes in this high‐risk cohort varied considerably with antenatal OGTT values, providing the opportunity for targeted intervention to prevent future diabetes.
The evolution of thyroid function with puberty Marwaha, Raman Kumar; Tandon, Nikhil; Desai, Ankush K. ...
Clinical endocrinology (Oxford),
June 2012, Letnik:
76, Številka:
6
Journal Article
Recenzirano
Summary
Objective This study was planned to describe thyroid functional status in different stages of puberty.
Study design We collected data from five schools across different geographical zones ...of Delhi. All children who consented were evaluated for anthropometry, pubertal stage, goitre status, serum free T3 (FT3), free T4 (FT4), TSH, anti‐TPO (thyroid peroxidase) antibodies and thyroid ultrasound. From this sample, a disease‐ and risk‐free or ‘reference population’ was obtained by excluding those with history of thyroid disease or use of thyroid medications, family history of thyroid disease, goitre, hypoechogenicity or nodularity on ultrasound or positive antithyroid antibodies.
Results The ‘total population’ comprised 3722 children; the ‘reference population’ comprised 2134 subjects. The mean, median, 3rd and 97th percentiles of serum FT3, FT4 and TSH for each stage of puberty were obtained. In both boys and girls, FT3 increased with entry into puberty and either stayed constant or declined marginally after stage 3 of puberty. In contrast, in both genders, FT4 decreased with entry into puberty and stayed relatively constant after stage 3 of puberty. TSH levels declined through puberty in boys, but remained largely unchanged in girls. An increased conversion of T4 to T3 is the possible explanation for this finding.
Conclusions This large community‐based study in school‐age children using strict exclusion criteria provides data of thyroid function in the various stages of puberty. There is no evidence of ‘thyroidarche’ during or preceding puberty.
This study was planned to obtain normative data of thyroid functions in school-age children from different regions of India.
Students from 36 schools involving 13 states across four geographical ...zones of India were evaluated for goiter. Subjects who consented, underwent evaluation for serum FT3, FT4, TSH, anti-TPO antibodies and thyroid ultrasound. From this, a “reference population” was obtained by excluding those with personal or family history of thyroid disease, use of thyroid medications, goiter, hypoechogenicity or nodularity on ultrasound or positive anti-thyroid antibodies.
Of 24,685 students clinically evaluated, 8665 formed part of the study. The reference population comprised 5343 subjects. The mean, median, 3rd and 97th percentiles of FT3, FT4 and TSH for each year (6–17 years) were obtained.
This community based study in Indian school-age children provides reference intervals for thyroid hormones and evidence against narrowing the TSH reference range.
Objective To report a patient with Bardet-Biedl syndrome (BBS) with known hypogonadotrophic hypogonadism who developed spontaneous reversal of hypogonadism in adulthood. Design Case report and ...discussion. Setting Endocrine unit of a tertiary hospital. Patient(s) A 30-year-old male patient with BBS. Intervention(s) Clinical evaluation, fine-needle aspiration of the testes, hormonal, cytogenetic, and pathologic evaluation. Main Outcome Measure(s) Serum gonadotropins and testosterone levels and presence of spermatogenesis in testicular aspirate. Result(s) Serum testosterone and gonadotropin levels were within the normal adult male range. Testicular aspirates showed spermatogenic cells of all series, including numerous spermatozoa and a few intact seminiferous tubules. The overall picture appeared to be consistent with normal spermatogenesis. Conclusion(s) This is the first case of reversal of hypogonadotrophic hypogonadism in a male patient with BBS. Clinicians should look for such reversal in other patients with hypogonadotrophic hypogonadism and give appropriate prognosis.
We present ULGEN, a runtime assurance (RTA) framework for programming safe cyber-physical systems (CPS). In ULGEN, a system is implemented as a collection of asynchronous processes executing RTA ...modules which are generalizations of the well-known Simplex architecture. An RTA module is composed of a set of safe controllers (SCs), designed to guarantee certain safety specifications, and a set of advanced controllers (ACs), optimized for performance, each defined to run under the specific conditions of the operating environment, and a decision module implementing the switching logic between the controllers. A source of complexity in achieving safe CPS is that these systems often involve concurrently interacting components with different execution semantics. To this end, ULGEN allows for the definition of RTA modules with either event-driven or time-driven execution semantics and encapsulates such components into RTA modules. It further provides primitives for implementing priority-based communication between asynchronous processes, which is a necessary feature for task prioritization mechanisms such as contingency plans and interrupt service routines. The framework also provides formal guarantees on the safe execution of RTA modules based on a formal definition of well-formedness. In ULGEN, a well-formed RTA module combines SCs and ACs in a way that guarantees the underlying safety specifications assured by the SCs while delivering the desired performance offered by the ACs. We compare the safety guarantees of ULGEN against other state-of-the-art RTA frameworks and demonstrate its efficacy in implementing safe and performant CPS by presenting an extensive experimental evaluation of five case studies both in a simulation environment and on a real robotic platform.
Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a ...multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia.
This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018.
We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings.
ClinicalTrials.gov: NCT01212328.
Verification of distributed systems using systematic exploration is daunting because of the many possible interleavings of messages and failures. When faced with this scalability challenge, existing ...approaches have traditionally mitigated state space explosion by avoiding exploration of redundant states (e.g., via state hashing) and redundant interleavings of transitions (e.g., via partial-order reductions). In this paper, we present an efficient symbolic exploration method that not only avoids redundancies in states and interleavings, but additionally avoids redundant computations that are performed during updates to states on transitions. Our symbolic explorer leverages a novel, fine-grained, canonical representation of distributed system configurations (states) to identify opportunities for avoiding such redundancies on-the-fly. The explorer also includes an interface that is compatible with abstractions for state-space reduction and with partial-order and other reductions for avoiding redundant interleavings. We implement our approach in the tool Psym and empirically demonstrate that it outperforms a state-of-the-art exploration tool, can successfully verify many common distributed protocols, and can scale to multiple real-world industrial case studies across
PDF
