Progression to microalbuminuria in type 1 diabetes: development and validation of a prediction rule

AIMS/HYPOTHESIS: Microalbuminuria is common in type 1 diabetes and is associated with an increased risk of renal and cardiovascular disease. We aimed to develop and validate a clinical prediction rule that estimates the absolute risk of microalbuminuria. METHODS: Data from the European Diabetes Prospective Complications Study (n = 1115) were used to develop the prediction rule (development set). Multivariable logistic regression analysis was used to assess the association between potential predictors and progression to microalbuminuria within 7 years. The performance of the prediction rule was assessed with calibration and discrimination (concordance statistic [c-statistic]) measures. The rule was validated in three other diabetes studies (Pittsburgh Epidemiology of Diabetes Complications [EDC] study, Finnish Diabetic Nephropathy [FinnDiane] study and Coronary Artery Calcification in Type 1 Diabetes [CACTI] study). RESULTS: Of patients in the development set, 13% were microalbuminuric after 7 years. Glycosylated haemoglobin, AER, WHR, BMI and ever smoking were found to be the most important predictors. A high-risk group (n = 87 [8%]) was identified with a risk of progression to microalbuminuria of 32%. Predictions showed reasonable discriminative ability, with c-statistic of 0.71. The rule showed good calibration and discrimination in EDC, FinnDiane and CACTI (c-statistic 0.71, 0.79 and 0.79, respectively). CONCLUSIONS/INTERPRETATION: We developed and validated a clinical prediction rule that uses relatively easily obtainable patient characteristics to predict microalbuminuria in patients with type 1 diabetes. This rule can help clinicians to decide on more frequent check-ups for patients at high risk of microalbuminuria in order to prevent long-term chronic complication

Stroke Complications in Patients Requiring Durable Mechanical Circulatory Support Systems After Extracorporeal Life Support

Stroke is one of the leading complications following durable mechanical circulatory support (MCS) implantation. The aim of this multicenter study was to investigate stroke complications in patients requiring durable MCS following extracorporeal life support (ECLS). Data of 11 high volume MCS centers were collected and evaluated to identify patients who underwent durable MCS implantation after ECLS support between January 2010 and August 2018. The primary outcome was stroke following durable MCS implantation. Univariate and multivariate logistic regression analyses were performed to determine predictors of stroke. Overall, 531 patients met the inclusion criteria. Only patients who were supported with continuous flow pumps were included in this study accounting for 495 patients (median age 54 years old [interquartile range 47-60]). A total of 136 patients (27%) developed postoperative stroke on device during the follow-up (48% ischemic and 52% hemorrhagic) after a median durable MCS support of 320 [32-1000] days, accounting for 0.17 events per patient-year. Of 133 patients with known date of stroke, a total of 47 (10%) developed stroke during the first 30 days (64% ischemic and 36% hemorrhagic), and 86 patients developed stroke after 30 days (38% ischemic and 62% hemorrhagic) of durable MCS support (late stroke). Survival rate was significantly lower in patients with hemorrhagic stroke (p = 0.00091). Stroke appears to be a common complication in patients transitioned to durable MCS support after ECLS. Hemorrhagic stroke is a more common type of late stroke and is associated with inferior outcomes

Transition From Temporary to Durable Circulatory Support Systems

BACKGROUND: The decision to implant durable mechanical circulatory systems (MCSs) in patients on extracorporeal life support (ECLS) is challenging due to expected poor outcomes in these patients. OBJECTIVES: The aim of this study was to identify outcome predictors that may facilitate future patient selection and decision making. METHODS: The Durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent MCS implantation after ECLS between January 2010 and August 2018 in 11 high-volume European centers. Several perioperative parameters were collected. The primary endpoint was survival at 1 year after durable MCS implantation. RESULTS: A total of 531 durable MCSs after ECLS were implanted during this period. The average patient age was 53 ± 12 years old. ECLS cannulation was peripheral in 87% of patients and 33% of the patients had history of cardiopulmonary resuscitation before ECLS implantation. The 30-day, 1-year, and 3-year actuarial survival rates were 77%, 53%, and 43%, respectively. The following predictors for 1-year outcome have been observed: age, female sex, lactate value, Model of End-Stage Liver Disease XI score, history of atrial fibrillation, redo surgery, and body mass index >30 kg/m2. On the basis of this data, a risk score and an app to estimate 1-year mortality was created. CONCLUSIONS: The outcome in patients receiving durable MCS after ECLS remains limited, yet preoperative factors may allow differentiating futile patients from those with significant survival benefit

Manufacturing classification system in the real world: factors influencing manufacturing process choices for filed commercial oral solid dosage formulations, case studies from industry and considerations for continuous processing

Following the first Manufacturing Classification System (MCS) paper, the team conducted surveys to establish which active pharmaceutical ingredient (API) properties were important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. The most commonly identified factors were (1) API particle size: small particle sizes are known to increase risk of processing issues; (2) Drug loading in the formulation: high drug loadings allow less opportunity to mitigate poor API properties through the use of excipients. The next step was to establish linkages with process decisions by identifying publicly-available proxies for these important parameters: dose (in place of drug loading) and BCS class (in place of particle size). Poorly-soluble API were seen as more likely to have controlled (smaller) particle size than more highly soluble API. Analysis of 435 regulatory filings revealed that higher doses and more poorly-soluble API was associated with more complex processing routes. Replacing the proxy factors with the original parameters should give the opportunity to demonstrate stronger trends. This assumption was tested by accessing a dataset relating to commercial tablet products. This showed that, for dry processes, a larger particle size was associated with higher achievable drug loading as determined by percolation threshold.</p

Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO multi-country survey of Maternal and Newborn Health

10.1111/1471-0528.14548BJOG: An International Journal of Obstetrics and Gynaecology12491346-135

Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO

OBJECTIVE: To evaluate the extent to which stillbirths affect international comparisons of preterm birth rates in low- and middle-income countries. DESIGN: Secondary analysis of a multi-country cross-sectional study. SETTING: 29 countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 258 215 singleton deliveries in 286 hospitals. METHODS: We describe how inclusion or exclusion of stillbirth affect rates of preterm births in 29 countries. MAIN OUTCOME MEASURES: Preterm delivery. RESULTS: In all countries, preterm birth rates were substantially lower when based on live births only, than when based on total births. However, the increase in preterm birth rates with inclusion of stillbirths was substantially higher in low Human Development Index (HDI) countries [median 18.2%, interquartile range (17.2-34.6%)] compared with medium (4.3%, 3.0-6.7%), and high-HDI countries (4.8%, 4.4-5.5%). CONCLUSION: Inclusion of stillbirths leads to higher estimates of preterm birth rate in all countries, with a disproportionately large effect in low-HDI countries. Preterm birth rates based on live births alone do not accurately reflect international disparities in perinatal health; thus improved registration and reporting of stillbirths are necessary. TWEETABLE ABSTRACT: Inclusion of stillbirths increases preterm birth rates estimates, especially in low-HDI countries