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.
Abstract Background Treatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a ...high-risk subset of survivors for early intervention. Objectives This study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies. Methods Echocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464). Results Only 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography–graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio RR: 1.38; 95% confidence interval CI: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m2 (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53). Conclusions Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.
Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically ...engineered mouse model (LSL-K-ras(G12D)) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-ras(G12D); Pdx-1cre) and their control unfloxed (LSL-K-ras(G12D)) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m(3)) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells (MDSCs) decreased significantly in floxed mice compared with unfloxed controls (P<0.01) after the smoke exposure with the concurrent increase in the macrophage (P<0.05) and dendritic cell (DCs) (P<0.01) population. Further, smoking-induced inflammation (IFN-γ, CXCL2; P<0.05) was accompanied by enhanced activation of pancreatic stellate cells and elevated levels of serum retinoic acid-binding protein 4, indicating increased bioavailability of retinoic acid which contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs) and DCs. TAMs predominantly contribute to the increased expression of heparin-binding epidermal growth factor-like growth factor (EGFR ligand) in pre-neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of the immune system early during PC progression. Overall, the present study provides a novel mechanism of smoking-induced increase in ADM in the presence of constitutively active K-ras mutation.
Summary Background Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy. However, these studies were small and not ...designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy. Methods This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir (18 F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov , number NCT 01447719 (original study NCT 00857415 ). Findings We included 59 participants (aged 47–103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78–98) and 100% (20 of 20; 80–100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80–100%) and 100% (18 of 18; 78–100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p<0·0001) and within 12 months between imaging and autopsy (0·79; p<0·0001). Interpretation The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density. Funding Avid Radiopharmaceuticals.
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than ...subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.
We describe the HadGEM2 family of climate configurations of the Met Office Unified Model, MetUM. The concept of a model "family" comprises a range of specific model configurations incorporating ...different levels of complexity but with a common physical framework. The HadGEM2 family of configurations includes atmosphere and ocean components, with and without a vertical extension to include a well-resolved stratosphere, and an Earth-System (ES) component which includes dynamic vegetation, ocean biology and atmospheric chemistry. The HadGEM2 physical model includes improvements designed to address specific systematic errors encountered in the previous climate configuration, HadGEM1, namely Northern Hemisphere continental temperature biases and tropical sea surface temperature biases and poor variability. Targeting these biases was crucial in order that the ES configuration could represent important biogeochemical climate feedbacks. Detailed descriptions and evaluations of particular HadGEM2 family members are included in a number of other publications, and the discussion here is limited to a summary of the overall performance using a set of model metrics which compare the way in which the various configurations simulate present-day climate and its variability.
To evaluate the performance characteristics of florbetapir F18 positron emission tomography (PET) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control ...subjects (HCs).
Florbetapir PET was acquired in 184 subjects (45 AD patients, 60 MCI patients, and 79 HCs) within a multicenter phase 2 study. Amyloid burden was assessed visually and quantitatively, and was classified as positive or negative.
Florbetapir PET was rated visually amyloid positive in 76% of AD patients, 38% of MCI patients, and 14% of HCs. Eighty-four percent of AD patients, 45% of MCI patients, and 23% of HCs were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and apolipoprotein E ε4 carrier status.
: The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate the potential value of florbetapir F18 PET as an adjunct to clinical diagnosis.
The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss ...of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively.
Summary
Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs’ mechanism of action includes ...promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5–36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and ‘high‐dose’ glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine‐related consequences of this novel class of immunotherapies.
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