Development of a postoperative delirium risk scoring tool using data from the Australian and New Zealand Hip Fracture Registry: an analysis of 6672 patients 2017-2018

Background and purposeThis study aimed to determine the incidence, predictors of postoperative delirium and develop a post-surgery delirium risk scoring tool.Patients and MethodsA total of 6672 hip fracture patients with documented assessment for delirium were analyzed from the Australia and New Zealand Hip Fracture Registry between June 2017 and December 2018.Thirty-six variables for the prediction of delirium using univariate and multivariate logistic regression were assessed. The models were assessed for diagnostic accuracy using C-statistic and calibration using Hosmer-Lemeshow goodness-of-fit test. A Delirium Risk Score was developed based on the regression coefficients.ResultsDelirium developed in 2599/6672 (39.0%) hip fracture patients. Seven independent predictors of delirium were identified; age above 80 years (OR=1.6 CI 1.4-1.9; p=0.001), male (OR=1.3 CI 1.1-1.5; p=0.007), absent pre-operative cognitive assessment (OR=1.5 CI 1.3-1.9; p=0.001), impaired pre-operative cognitive state (OR=1.7 CI 1.3 -2.1; p=0.001), surgery delay (OR=1.7 CI 1.2-2.5; p=0.002) and mobilisation day 1 post-surgery (OR=1.9 CI 1.4-2.6; p=0.001). The C-statistics for the training and validation datasets were 0.74 and 0.75, respectively. Calibration was good (χ2=35.72 (9); p<0.001). The Delirium Risk Score for patients ranged from 0 to 42 in the validation data and when used alone as a risk predictor, had similar levels of diagnostic accuracy (C-statistic=0.742) indicating its potential for use as a stand-alone risk scoring tool.ConclusionWe have designed and validated a delirium risk score for predicting delirium following surgery for a hip fracture using seven predicting factors. This could assist clinicians in identifying high risk patients requiring higher levels of observation and post-surgical care.     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study

BackgroundPneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh.MethodsWe conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3–35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression.ResultsWe matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, −0.2%, 38.4%) for ≥2 PCV10 doses and among 3–11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, −22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls.ConclusionsClinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment – compared to clinic controls – was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs.     

Devil in disguise: Does drinking lead to a disability pension?

ObjectivesTo examine whether alcohol consumption in adulthood is related to the incidence of receiving a disability pension later in life.MethodsTwin data for Finnish men and women born before 1958 were matched to register-based individual information on disability pensions. Twin differences were used to eliminate both shared environmental and genetic factors. The quantity of alcohol consumption was measured as the weekly average consumption using self-reported data from three surveys (1975, 1981 and 1990). The disability pension data were evaluated from 1990–2004.ResultsThe models that account for shared environmental and genetic factors reveal that heavy drinkers are significantly more likely to receive a disability pension than moderate drinkers or constant abstainers. Heavy drinking that leads to passing out is also positively related to receiving a disability pension. The results were robust to the use of potential confounders that twins do not share, such as education years, the number of chronic diseases, physical activity at work and leisure, and stressful life events.ConclusionDrinking profiles in early adulthood are an important predictor of receiving a disability pension later in life.