There is limited information characterizing young adults (18–35 years) (YA) with diabetes, especially those admitted for hyperglycemic emergencies. The study aims were to examine associations of ...patient-level characteristics with hyperglycemic emergency hospitalization and to identify variations based on diabetes type and glycemic control.
We conducted retrospective analysis of 273 YA admitted to an inner-city hospital with diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHS). T-tests, Chi-Square tests, and ANOVA identified differences in demographics, diabetes history, clinical indicators, complications/comorbidities, and hospital admission stratified separately by diabetes type (1 vs 2) and admission HbA1c < 9% (75 mmol/mol), ≥9% to 12% (108 mmol/mol), ≥12%).
Mean admission HbA1c was 12.4% (112 mmol/ml). HbA1c was ≥9.0% for 90.5%. The main DKA/HHS trigger was medication nonadherence (57.9%), with 35.6% presenting with new-onset type 2 diabetes. Only 3.7% utilized outpatient diabetes clinics, 38.8% were re-hospitalized within the year, and 69% lacked insurance. Diabetes complications (44.7%) and psychiatric co-morbidities (35.5%) were common. Significantly more YA with type 1 diabetes had insurance, whereas YA with type 2 diabetes had higher admission HbA1c. YA with HbA1c ≥12% were more likely to be Black and lack insurance.
YA hospitalized for DKA/HHS in an inner-city hospital tended to have severely uncontrolled diabetes. Many already had comorbidities and diabetes complications, high use of acute care services and low use of diabetes specialty services. YA characteristics varied by diabetes type and HbA1c. Overall, a substantial percentage lacked insurance, potentially impacting healthcare utilization patterns and medication adherence, and leading to DKA/HHS admissions.
To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, ...hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).
We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.
The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.
This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.
Diabetes is an important contributor to global morbidity and mortality. The contributions of population aging and macroeconomic changes to the growth in diabetes prevalence over the past 20 years are ...unclear.
We used cross-sectional data on age- and sex-specific counts of people with diabetes by country, national population estimates, and country-specific macroeconomic variables for the years 1990, 2000, and 2008. Decomposition analysis was performed to quantify the contribution of population aging to the change in global diabetes prevalence between 1990 and 2008. Next, age-standardization was used to estimate the contribution of age composition to differences in diabetes prevalence between high-income (HIC) and low-to-middle-income countries (LMICs). Finally, we used non-parametric correlation and multivariate first-difference regression estimates to examine the relationship between macroeconomic changes and the change in diabetes prevalence between 1990 and 2008.
Globally, diabetes prevalence grew by two percentage points between 1990 (7.4 %) and 2008 (9.4 %). Population aging was responsible for 19 % of the growth, with 81 % attributable to increases in the age-specific prevalences. In both LMICs and HICs, about half the growth in age-specific prevalences was from increasing levels of diabetes between ages 45-65 (51 % in HICs and 46 % in LMICs). After age-standardization, the difference in the prevalence of diabetes between LMICs and HICs was larger (1.9 % point difference in 1990; 1.5 % point difference in 2008). We found no evidence that macroeconomic changes were associated with the growth in diabetes prevalence.
Population aging explains a minority of the recent growth in global diabetes prevalence. The increase in global diabetes between 1990 and 2008 was primarily due to an increase in the prevalence of diabetes at ages 45-65. We do not find evidence that basic indicators of economic growth, development, globalization, or urbanization were related to rising levels of diabetes between 1990 and 2008.
Background An estimated 150,000 pulmonary nodules are identified each year, and the number is likely to increase given the results of the National Lung Screening Trial. Decision tools are needed to ...help with the management of such pulmonary nodules. We examined whether adding any of three novel functions of nodule volume improves the accuracy of an existing malignancy prediction model of CT scan-detected nodules. Methods Swensen's 1997 prediction model was used to estimate the probability of malignancy in CT scan-detected nodules identified from a sample of 221 patients at the Medical University of South Carolina between 2006 and 2010. Three multivariate logistic models that included a novel function of nodule volume were used to investigate the added predictive value. Several measures were used to evaluate model classification performance. Results With use of a 0.5 cutoff associated with predicted probability, the Swensen model correctly classified 67% of nodules. The three novel models suggested that the addition of nodule volume enhances the ability to correctly predict malignancy; 83%, 88%, and 88% of subjects were correctly classified as having malignant or benign nodules, with significant net improved reclassification for each ( P < .0001). All three models also performed well based on Nagelkerke R2 , discrimination slope, area under the receiver operating characteristic curve, and Hosmer-Lemeshow calibration test. Conclusions The findings demonstrate that the addition of nodule volume to existing malignancy prediction models increases the proportion of nodules correctly classified. This enhanced tool will help clinicians to risk stratify pulmonary nodules more effectively.
Mixing matrices quantify how people with similar or different characteristics make contact with each other, creating potential for disease transmission. Little empirical data on mixing patterns among ...persons who inject drugs (PWID) are available to inform models of blood-borne disease such as HIV and hepatitis C virus. Egocentric drug network data provided by PWID in Baltimore, Maryland between 2005 and 2007 were used to characterise drug equipment-sharing patterns according to age, race and gender. Black PWID and PWID who were single (i.e. no stable sexual partner) self-reported larger equipment-sharing networks than their white and non-single counterparts. We also found evidence of assortative mixing according to age, gender and race, though to a slightly lesser degree in the case of gender. Highly assortative mixing according to race and gender highlights the existence of demographically isolated clusters, for whom generalised treatment interventions may have limited benefits unless targeted directly. These findings provide novel insights into mixing patterns of PWID for which little empirical data are available. The age-specific assortativity we observed is also significant in light of its role as a key driver of transmission for other pathogens such as influenza and tuberculosis.
Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not ...known.
We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.
A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval CI, 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).
Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).
We sought to evaluate the prognostic impact of right ventricular (RV) myocardial involvement in patients with inferior myocardial infarction (MI).
There is uncertainty regarding the risk of major ...complications in patients with inferior MI complicated by RV myocardial involvement. Whether these complications are related to RV myocardial involvement itself or simply to the extent of infarction involving the left ventricle (LV) is also unknown.
We examined the incidence of death and mechanical and electrical complications in patients with (n = 491) and without (n = 638) RV myocardial involvement and in patients with anterior MI (n = 971) in an analysis from the Collaborative Organization for RheothRx Evaluation (CORE) trial. Left ventricular infarct size was assessed by technetium-99m-sestamibi single-photon emission computed tomography and peak creatine kinase, and LV function was assessed by radionuclide angiography. We also performed a meta-analysis in which we pooled the results of our study with previous smaller studies addressing the same question.
Six-month mortality was 7.8% in inferior MI compared with 13.2% in anterior MI. Among patients with inferior MI, serious arrhythmias were significantly more common in patients with RV myocardial involvement who also had a trend toward higher mortality, pump failure and mechanical complications. However, this was not associated with a difference in LV infarct size or function. A meta-analysis of six studies (n = 1,198) confirmed that RV myocardial involvement was associated with an increased risk of death (odds ratio OR 3.2, 95% confidence interval CI 2.4 to 4.1), shock (OR 3.2, 95% CI 2.4 to 3.5), ventricular tachycardia or fibrillation (OR 2.7, 95% CI 2.1 to 3.5) and atrioventricular block (OR 3.4, 95% CI 2.7 to 4.2).
Patients with inferior MI who also have RV myocardial involvement are at increased risk of death, shock and arrhythmias. This increased risk is related to the presence of RV myocardial involvement itself rather than the extent of LV myocardial damage.
To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, ...hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA).
We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations.
The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality.
This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.
Mutations in the gene ATM are responsible for the genetic disorder ataxia-telangiectasia (A-T), which is characterized by cerebellar dysfunction, radiosensitivity, chromosomal instability and cancer ...predisposition. Both the A-T phenotype and the similarity of the ATM protein to other DNA-damage sensors suggests a role for ATM in biochemical pathways involved in the recognition, signalling and repair of DNA double-strand breaks (DSBs). There are strong parallels between the pattern of radiosensitivity, chromosomal instability and cancer predisposition in A-T patients and that in patients with Nijmegen breakage syndrome (NBS). The protein defective in NBS, nibrin (encoded by NBS1), forms a complex with MRE11 and RAD50 (refs 1,2). This complex localizes to DSBs within 30 minutes after cellular exposure to ionizing radiation (IR) and is observed in brightly staining nuclear foci after a longer period of time. The overlap between clinical and cellular phenotypes in A-T and NBS suggests that ATM and nibrin may function in the same biochemical pathway. Here we demonstrate that nibrin is phosphorylated within one hour of treatment of cells with IR. This response is abrogated in A-T cells that either do not express ATM protein or express near full-length mutant protein. We also show that ATM physically interacts with and phosphorylates nibrin on serine 343 both in vivo and in vitro. Phosphorylation of this site appears to be functionally important because mutated nibrin (S343A) does not completely complement radiosensitivity in NBS cells. ATM phosphorylation of nibrin does not affect nibrin-MRE11-RAD50 association as revealed by radiation-induced foci formation. Our data provide a biochemical explanation for the similarity in phenotype between A-T and NBS.
Background. In Western countries, incidence of thrombocytopenia in intensive care units (ICUs) has been found to be 13 - 44%. We chose to study the incidence, risk factors and transfusion ...requirements of thrombocytopenia in tertiary care ICUs in northern India. Objective. To study the incidence and risk factors of thrombocytopenia in a mixed ICU. Methods. This prospective observational 6-month cohort study was conducted in two 22-bedded medical-surgical ICUs. Patients aged 18 years or older with an ICU stay of at least 2 days were included. Results. Thrombocytopenia (<150 000/dL) occurred in 190 (38%) of the 500 patients studied. Thrombocytopenia was present on admission in 41 (8%) patients. Of the remaining patients, 149 (32%) developed new-onset thrombocytopenia (NOT) - thrombocytopenia developing in patients with platelet count more than 150 000/U on admission - during ICU stay. Incidence and prevalence were 30% and 38%, respectively. ICU mortality was 13%. Thrombocytopenia was commonly associated with sepsis, disseminated intravascular coagulation, heparin and certain antibiotics. Cause could not be established in 10 patients. Underlying coronary artery disease and sepsis correlated with thrombocytopenia. Mortality was higher in patients with NOT (15.4 v. 8.7%, p=0.003). Compared with non-thrombocytopenic patients, patients with NOT required more blood product transfusions (57.7 v. 38.4%, p=0.000) and mechanical ventilation (23.5 v. 13.5%, p=0.008). No difference was observed in length of hospital stay and bleeding risk between the two groups. Conclusion. We found incidence and prevalence of thrombocytopenia in the ICU comparable with internationally reported figures. NOT was associated with higher mortality and morbidity and may be considered as a marker of disease severity.
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