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Measurement of Peak C-Peptide at Diagnosis Informs Glycemic Control but not Hypoglycemia in Adults With Type 1 Diabetes.
No full textContext
High-residual C-peptide in longer-duration type 1 diabetes (T1D) is associated with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close to diagnosis.
Objective
Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with T1D, we aimed to explore if variation in C-peptide close to diagnosis influenced glycemic variability and risk of hypoglycemia.
Methods
We studied newly diagnosed adults with T1D who wore a Dexcom G4 CGM for 7 days as part of the Exercise in Type 1 Diabetes (EXTOD) study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants.
Results
For every 100 pmol/L-increase in peak C-peptide, the percentage of time spent in the range 3.9 to 10 mmol/L increased by 2.4% (95% CI, 0.5-4.3), = .01) with a reduction in time spent at level 1 hyperglycemia (> 10 mmol/L) and level 2 hyperglycemia (> 13.9 mmol/L) by 2.6% (95% CI, -4.9 to -0.4, = .02) and 1.3% (95% CI, -2.7 to -0.006, = .04), respectively. Glucose levels were on average lower by 0.19 mmol/L (95% CI, -0.4 to 0.02, = .06) and SD reduced by 0.14 (95% CI, -0.3 to -0.02, = .02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia ( = .97) or hypoglycemic risk ( = .72). There was no association between peak C-peptide and insulin dose-adjusted glycated hemoglobin A ( = .45).
Conclusion
C-peptide is associated with time spent in the normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with T1D
Accuracy and cost-effectiveness of different screening strategies for identifying undiagnosed COPD among primary care patients (≥40 years) in China: a cross-sectional screening test accuracy study: findings from the Breathe Well group.
No full textOBJECTIVES
To examine the accuracy and cost-effectiveness of various chronic obstructive pulmonary disease (COPD) screening tests and combinations within a Chinese primary care population.
DESIGN
Screening test accuracy study.
SETTING
Urban and rural community health centres in four municipalities of China: Beijing (north), Chengdu (southwest), Guangzhou (south) and Shenyang (northeast).
PARTICIPANTS
Community residents aged 40 years and above who attended community health centres for any reason were invited to participate. 2445 participants (mean age 59.8 (SD 9.6) years, 39.1% (n=956) male) completed the study (February-December 2019), 68.9% (n=1684) were never-smokers and 3.6% (n=88) had an existing COPD diagnosis. 13.7% (n=333) of participants had spirometry-confirmed airflow obstruction.
INTERVENTIONS
Participants completed six index tests (screening questionnaires (COPD Diagnostic Questionnaire, COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE), Chinese Symptom-Based Questionnaire (C-SBQ), COPD-SQ), microspirometry (COPD-6), peak flow (model of peak flow meters used in the study (USPE)) and the reference test (ndd Easy On-PC).
PRIMARY AND SECONDARY OUTCOMES
Cases were defined as those with forced expiratory volume in one second (FEV)/forced vital capacity (FVC) below the lower limit of normal (LLN-GLI) on the reference test. Performance of individual screening tests and their combinations was evaluated, with cost-effectiveness analyses providing cost per additional true case detected.
RESULTS
Airflow measurement devices (sensitivities 64.9% (95% CI 59.5% to 70.0%) and 67.3% (95% CI 61.9% to 72.3%), specificities 89.7% (95% CI 88.4% to 91.0%) and 82.6% (95% CI 80.9% to 84.2%) for microspirometry and peak flow, respectively) generally performed better than questionnaires, the most accurate of which was C-SBQ (sensitivity 63.1% (95% CI 57.6% to 68.3%) specificity 74.2% (95% CI 72.3% to 76.1%)). The combination of C-SBQ and microspirometry used in parallel maximised sensitivity (81.4%) (95% CI 76.8% to 85.4%) and had specificity of 68.0% (95% CI 66.0% to 70.0%), with an incremental cost-effectiveness ratio of £64.20 (CNY385) per additional case detected compared with peak flow.
CONCLUSIONS
Simple screening tests to identify undiagnosed COPD within the primary care setting in China is possible, and a combination of C-SBQ and microspirometry is the most sensitive and cost-effective. Further work is required to explore optimal cut-points and effectiveness of programme implementation.
TRIAL REGISTRATION NUMBER
ISRCTN13357135
Undifferentiated and dedifferentiated soft tissue neoplasms: Immunohistochemical surrogates for differential diagnosis.
No full textUndifferentiated soft tissue sarcomas (USTS) are described in the current World Health Organization Classification of Soft Tissue and Bone Tumours as those showing no identifiable line of differentiation when analyzed by presently available technologies. This is a markedly heterogeneous group, and the diagnosis of USTS remains one of exclusion. USTS can be divided into four morphologic subgroups: pleomorphic, spindle cell, round cell and epithelioid undifferentiated sarcomas, with this combined group accounting for up to 20% of all soft tissue sarcomas. As molecular advances enable the stratification of emerging genetic subsets within USTS, particularly within undifferentiated round cell sarcomas, other groups, particularly the category of undifferentiated pleomorphic sarcomas (UPS), still remain difficult to substratify and represent heterogeneous collections of neoplasms often representing the common morphologic endpoints of a variety of malignant tumors of various (mesenchymal and non-mesenchymal) lineages. However, recent molecular developments have also enabled the identification and correct classification of many tumors from various lines of differentiation that would previously have been bracketed under 'UPS'. This includes pleomorphic neoplasms and dedifferentiated neoplasms (the latter typically manifesting with an undifferentiated pleomorphic morphology) of mesenchymal (e.g. solitary fibrous tumor and gastrointestinal stromal tumor) and non-mesenchymal (e.g. melanoma and carcinoma) origin. The precise categorization of 'pleomorphic' or 'undifferentiated' neoplasms is critical for prognostication, as, for example, dedifferentiated liposarcoma typically behaves less aggressively than other pleomorphic sarcomas, and for management, including the potential for targeted therapies based on underlying recurrent molecular features. In this review we focus on undifferentiated and dedifferentiated pleomorphic and spindle cell neoplasms, summarizing their key genetic, morphologic and immunophenotypic features in the routine diagnostic setting, and the use of immunohistochemistry in their principal differential diagnosis, and highlight new developments and entities in the group of undifferentiated and dedifferentiated soft tissue sarcomas
ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.
No full textThis is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimization, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC
Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension.
No full textOBJECTIVE
Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.
METHODS
IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.
RESULTS
Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).
CONCLUSIONS
We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.
TRIAL REGISTRATION
This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486
Heat illness experience at BMH Shaibah, Basra, during Operation TELIC: May-July 2003.
No full textThis is an observational study of heat-related illness in UK Service Personnel deployed into summer conditions in Northern Kuwait and Southern Iraq. Among 622 hospitalisations reported during a 9-week period at the historical British Military Hospital, Shaibah, 303 consecutive admissions are reviewed in detail. Several clinical syndromes attributable to thermal stress were observed. These ranged from self-limiting debility to life-threatening failures of homeostasis, with 5.0% developing a critical care requirement. Hyponatraemia was a commonly occurring electrolyte disturbance by which, relative to the local reference range, a majority of heat-attributed admissions were affected. Reductions in measured serum sodium could be profound (<125 mmol/L in 20.1% of all heat-related casualties). Hypokalaemia was observed in half of cases, though only a minority were affected by severely low potassium (<2.5 mmol/L in 4.0%). Despite preventive measures prescribed on hospital discharge, illness and significant biochemical derangements could recur upon return to duties in the heat. We reiterate the need for primary prevention of heat illness wherever possible and importance of early, effective interventions to treat and protect Service Personnel from secondary injury. We also highlight the requirement for comprehensive assessment to inform prognostication and occupational decision-making in relation to extreme climatic heat, including aeromedical evacuation. We draw additional attention to the contribution of psychological factors in select cases and identify research questions to improve understanding of environment-induced incapacitation in general
Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis.
No full textBackground
Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.
Methods
Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.
Results
Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP.
Conclusions
This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets
The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation.
No full textHigh-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0-10. Low-risk (0-3), medium-risk (4-5), and high-risk (6-10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8-60.7%), 46.3% (95% CI 41.1-51.4%), and 32.1% (95% CI 23.5-41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT
European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision.
No full textOBJECTIVE
To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
METHODS
Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs).
RESULTS
Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point)