Aims/hypothesis
This study reports the results of the first phase of a national study to determine the prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose ...tolerance) in India.
Methods
A total of 363 primary sampling units (188 urban, 175 rural), in three states (Tamilnadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were sampled using a stratified multistage sampling design to survey individuals aged ≥20 years. The prevalence rates of diabetes and prediabetes were assessed by measurement of fasting and 2 h post glucose load capillary blood glucose.
Results
Of the 16,607 individuals selected for the study, 14,277 (86%) participated, of whom 13,055 gave blood samples. The weighted prevalence of diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were 8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis showed that age, male sex, family history of diabetes, urban residence, abdominal obesity, generalised obesity, hypertension and income status were significantly associated with diabetes. Significant risk factors for prediabetes were age, family history of diabetes, abdominal obesity, hypertension and income status.
Conclusions/interpretations
We estimate that, in 2011, Maharashtra will have 6 million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand will have 0.96 million with diabetes and 1.5 million with prediabetes, and Chandigarh will have 0.12 million with diabetes and 0.13 million with prediabetes. Projections for the whole of India would be 62.4 million people with diabetes and 77.2 million people with prediabetes.
Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of ...antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as “responders”, experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.
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•Antiretroviral therapy for 24 weeks decreased HERV-K (HML-2) levels in most patients with ALS.•A rebound in HML-2 levels occurred after discontinuation of the antiretroviral drugs.•Patients that had an antiviral effect against HML-2 showed a trend for slower progression in several clinical parameters.
Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and ...inter-regional variations.
The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines.
A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1.
The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India.
Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.
The detection of new subtle brain pathology on MR imaging is a time-consuming and error-prone task for the radiologist. This article introduces and evaluates an image-registration and subtraction ...method for highlighting small changes in the brain with a view to minimizing the risk of missed pathology and reducing fatigue.
We present a fully automated algorithm for highlighting subtle changes between multiple serially acquired brain MR images with a novel approach to registration and MR imaging bias field correction. The method was evaluated for the detection of new lesions in 77 patients undergoing cardiac surgery, by using pairs of fluid-attenuated inversion recovery MR images acquired 1-2 weeks before the operation and 6-8 weeks postoperatively. Three radiologists reviewed the images.
On the basis of qualitative comparison of pre- and postsurgery FLAIR images, radiologists identified 37 new ischemic lesions in 22 patients. When these images were accompanied by a subtraction image, 46 new ischemic lesions were identified in 26 patients. After we accounted for interpatient and interradiologist variability using a multilevel statistical model, the likelihood of detecting a lesion was 2.59 (95% CI, 1.18-5.67) times greater when aided by the subtraction algorithm (
= .017). Radiologists also reviewed the images significantly faster (
< .001) by using the subtraction image (mean, 42 seconds; 95% CI, 29-60 seconds) than through qualitative assessment alone (mean, 66 seconds; 95% CI, 46-96 seconds).
Use of this new subtraction algorithm would result in considerable savings in the time required to review images and in improved sensitivity to subtle focal pathology.
Intravenous busulfan combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic haemopoietic cell transplantation (HCT). The best method to estimate busulfan ...exposure and optimum exposure in children or young adults remains unclear. We therefore assessed three approaches to estimate intravenous busulfan exposure (expressed as cumulative area under the curve AUC) and associated busulfan AUC with clinical outcomes in children or young adults undergoing allogeneic HCT.
In this retrospective analysis, patients from 15 centres in the Netherlands, USA, Canada, Switzerland, UK, Italy, Germany, and Australia who received a busulfan-based conditioning regimen between March 18, 2001, and Feb 12, 2015, were included. Cumulative AUC was calculated by numerical integration using non-linear mixed effect modelling (AUC
), non-compartmental analysis (AUC from 0 to infinity AUC
and to the next dose AUC
), and by individual centres using various approaches (AUC
). The main outcome of interest was event-free survival. Other outcomes of interest were graft failure or relapse, or both; transplantation-related mortality; acute toxicity (veno-occlusive disease or acute graft versus-host disease GvHD); chronic GvHD; overall survival; and chronic-GvHD-free event-free survival. We used propensity-score-adjusted Cox proportional hazard models, Weibull models, and Fine-Gray competing risk regressions for statistical analyses.
790 patients were enrolled, 674 of whom were included: 274 (41%) with malignant and 400 (59%) with non-malignant disease. Median age was 4·5 years (IQR 1·4-10·7). The median busulfan AUC
was 74·4 mg × h/L (95% CI 31·1-104·6), which correlated with the standardised method AUC
(r
=0·74), but the latter correlated poorly with AUC
(r
=0·35). Estimated 2-year event-free survival was 69·7% (95% CI 66·2-73·0). Event-free survival at 2 years was 77·0% (95% CI 72·1-82·9) in the 257 patients with an optimum intravenous busulfan AUC of 78-101 mg × h/L compared with 66·1% (60·9-71·4) in the 235 patients at the low historical target of 58-86 mg × h/L and 49·5% (29·2-66·0) in the 44 patients with a high (>101 mg × h/L) busulfan AUC (p=0·011). Compared with the low AUC group, graft failure or relapse occurred less frequently in the optimum AUC group (hazard ratio HR 0·57, 95% CI 0·39-0·84; p=0·0041). Acute toxicity (HR 1·69, 1·12-2·57; p=0·013) and transplantation-related mortality (2·99, 1·82-4·92; p<0·0001) were significantly higher in the high AUC group (>101 mg × h/L) than in the low AUC group (<78 mg × h/L), independent of indication; no difference was noted between AUC groups for chronic GvHD (<78 mg × h/L vs ≥78 mg × h/L, HR 1·30, 95% CI 0·73-2·33; p=0·37).
Improved clinical outcomes are likely to be achieved by targeting the busulfan AUC to 78-101 mg × h/L using a new validated pharmacokinetic model for all indications.
Research Allocation Program and the UCSF Helen Friller Family Comprehensive Cancer Center and the Mt Zion Health Fund of the University of California, San Francisco.
International Ocean Discovery Program (IODP) Expedition 359 cored sediments from eight borehole locations in the carbonate platform of the Maldives in the Indian Ocean. The expedition set out to ...unravel the timing of Neogene climate changes, in particular the evolution of the South Asian monsoon and fluctuations of the sea level. The timing of these changes are assessed by dating resultant sedimentary alterations that mark stratigraphic turning points in the Neogene Maldives platform system. The first four turning points during the early and middle Miocene are related to sea-level changes. These are reliably recorded in the stratigraphy of the carbonate sequences in which sequence boundaries provide the ages of the sea-level lowstand. Phases of aggradational platform growth give precise age brackets of long-term sea-level high stands during the early Miocene and the early to middle Miocene Climate Optimum that is dated here between 17 to 15.1 Ma. The subsequent middle Miocene cooling coincident with the eastern Antarctic ice sheet expansion resulted in a long-term lowering of sea level that is reflected by a progradational platform growth. The change in platform architecture from aggradation to progradation marks this turning point at 15.1 Ma.
An abrupt change in sedimentation pattern is recognized across the entire archipelago at a sequence boundary dated as 12.9–13 Ma. At this turning point, the platform sedimentation switched to a current-controlled mode when the monsoon-wind-driven circulation started in the Indian Ocean. The similar age of the onset of drift deposition from monsoon-wind-driven circulation across the entire archipelago indicates an abrupt onset of monsoon winds in the Indian Ocean. Ten unconformities dissect the drift sequences, attesting changes in current strength or direction that are likely caused by the combined product of changes in the monsoon-wind intensity and sea level fluctuations in the last 13 Ma. A major shift in the drift packages is dated with 3.8 Ma that coincides with the end of stepwise platform drowning and a reduction of the oxygen minimum zone in the Inner Sea.
The strata of the Maldives platform provides a detailed record of the extrinsic controlling factors on carbonate platform growth through time. This potential of carbonate platforms for dating the Neogene climate and current changes has been exploited in other platforms drilled by the Ocean Drilling Program. For example, Great Bahama Bank, the Queensland Plateau, and the platforms on the Marion Plateau show similar histories with sediment architectures driven by sea level in their early history (early to middle Miocene) replaced by current-driven drowning or partial drowning during their later history (Late Miocene). In all three platform systems, the influence of currents on sedimentations is reported between 11 and 13 Ma.
•This study is one of the first RCTs to assess the efficacy of a CBT-based antenatal Guided Self-Help intervention for pregnant women diagnosed with depression.•This RCT found that Guided Self-Help ...can be successfully delivered to depressed women in early pregnancy.•This antenatal Guided Self-Help intervention signalled improvements in women's depressive symptoms post-treatment.•The findings of this RCT suggest that an antenatal Guided Self-Help is suitable for use in talking therapy services.
Depression is a common antenatal mental disorder associated with significant maternal morbidity and adverse fetal outcomes. However, there is a lack of research on the effectiveness or cost-effectiveness of psychological interventions for antenatal depression.
A parallel-group, exploratory randomised controlled trial across five hospitals. The trial compared Guided Self-Help, modified for pregnancy, plus usual care with usual care alone for pregnant women meeting DSM-IV criteria for mild-moderate depression. The trial objectives were to establish recruitment/follow-up rates, compliance and acceptability, and to provide preliminary evidence of intervention efficacy and cost-effectiveness. The primary outcome of depressive symptoms was assessed by blinded researchers using the Edinburgh Postnatal Depression Scale at 14-weeks post-randomisation.
620 women were screened, 114 women were eligible and 53 (46.5%) were randomised. 26 women received Guided Self-Help – 18 (69%) attending ≥4 sessions - and 27 usual care; n = 3 women were lost to follow-up (follow-up rate for primary outcome 92%). Women receiving Guided Self-Help reported fewer depressive symptoms at follow-up than women receiving usual care (adjusted effect size −0.64 (95%CI: −1.30, 0.06) p = 0.07). There were no trial-related adverse events. The cost-effectiveness acceptability curve showed the probability of Guided Self-Help being cost-effective compared with usual care ranged from 10 to 50% with a willingness-to-pay range from £0 to £50,000.
Despite intense efforts we did not meet our anticipated recruitment target. However, high levels of acceptability, a lack of adverse events and a trend towards improvements in symptoms of depression post-treatment indicates this intervention is suitable for talking therapy services.
We have identified conditions for forming cultured human umbillical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo ...remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize into cords with early lumena by 24 h and then apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display HUVEC-lined thin-walled microvessels within the gel 31 days after implantation. Retroviral-mediated overexpression of a caspase-resistant Bcl-2 protein delays HUVEC apoptosis in vitro for over 7 days. Bcl-2-transduced HUVEC produce an increased density of HUVEC-lined perfused microvessels in vivo compared with untransduced or control-transduced HUVEC. Remarkably, Bcl-2- but not control-transduced HUVEC recruit an ingrowth of perivascular smooth-muscle α -actin-expressing mouse cells at 31 days, which organize by 60 days into HUVEC-lined multilayered structures resembling true microvessels. This system provides an in vivo model for dissecting mechanisms of microvascular remodeling by using genetically modified endothelium. Incorporation of such human endothelial-lined microvessels into engineered synthetic skin may improve graft viability, especially in recipients with impaired angiogenesis.
Chronic obstructive pulmonary disease (COPD) is common among non-smokers exposed to solid fuel combustion at home. Different clinical characteristics in these patients may have significant ...therapeutic and prognostic implications.
We used medical record review and a questionnaire among COPD patients at 15 centres across India to capture data on demographic details, different types of exposures and clinical characteristics. Chest radiography and pulmonary function testing were performed in all 1984 cases; C-reactive protein and exhaled breath nitric oxide were measured wherever available.
There were 1388 current or ex-smokers and 596 (30.0%) non-smokers who included 259 (43.5%) male and 337 (56.5%) female patients. Sputum production was significantly more common in smokers with COPD (
< 0.05). The frequency of acute symptomatic worsening, emergency visits and hospitalisation were significantly higher (
< 0.05) in non-smokers with COPD; however, intensive care unit admissions were similar in the two groups. There was no significant difference with respect to the use of bronchodilators, inhalational steroids or home nebulisation among smoker and non-smoker patients. The mean predicted forced expiratory volume in 1 sec in smokers (43.1%) was significantly lower than in non-smokers (46.5%).
Non-smoker COPD, more commonly observed in women exposed to biomass fuels, was characterised by higher rate of exacerbations and higher healthcare resource utilisation.
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